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Cited by 85Retinal Diseases and TreatmentsRetinal Development and DisordersAutophagy in Disease and Therapy

Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis

Open access
Jiang, Mei, Esteve-Rudd, Julian, Lopes, Vanda S., Diemer, Tanja, Lillo, Concepción, Rump, Agrani, Williams, David S.·2015·Journal of Cell Biology
DOI 10.1083/jcb.201410112PMC PMC4539993
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Abstract

The degradation of phagosomes, derived from the ingestion of photoreceptor outer segment (POS) disk membranes, is a major role of the retinal pigment epithelium (RPE). Here, POS phagosomes were observed to associate with myosin-7a, and then kinesin-1, as they moved from the apical region of the RPE. Live-cell imaging showed that the phagosomes moved bidirectionally along microtubules in RPE cells, with kinesin-1 light chain 1 (KLC1) remaining associated in both directions and during pauses. Lack of KLC1 did not inhibit phagosome speed, but run length was decreased, and phagosome localization and degradation were impaired. In old mice, lack of KLC1 resulted in RPE pathogenesis that was strikingly comparable to aspects of age-related macular degeneration (AMD), with an excessive accumulation of RPE and sub-RPE deposits, as well as oxidative and inflammatory stress responses. These results elucidate mechanisms of POS phagosome transport in relation to degradation, and demonstrate that defective microtubule motor transport in the RPE leads to phenotypes associated with AMD.

AI snapshot

Written from the paper’s full text.

TL;DR

In mouse RPE, POS phagosomes move bidirectionally along microtubules, with MYO7A associated with early apical phagosomes and KLC1 with later cell-body phagosomes; loss of KLC1 impairs phagosome motility, basal migration, and degradation. Aged *Klc1−/−* mice develop AMD-like retinal pathology, including lipofuscin accumulation, Bruch’s membrane thickening, oxidative stress, and complement activation.

Key findings

  • MYO7A was associated with 87 ± 3% of mAb1D4-labeled early phagosomes, whereas KLC1 was associated with only 12 ± 2% (n = 10 each); apical phagosomes associated more with MYO7A, and cell-body phagosomes more with KLC1. Kinesin-2 components were not detected on phagosomes, and *Kif3a* loss did not alter degradation.
  • In *Klc1−/−* RPE, segmental velocities were comparable to WT, but run lengths were shorter in plus-end (P = 0.02) and minus-end (P = 0.03) directions, reversal frequency was greater (P = 0.01), and the WT plus-end net-displacement bias was lost (P = 0.03). Basal migration was impaired: more phagosomes remained apical in vivo 3 h after light onset (P = 0.0002), and degradation was slowed, with more ingested POS remaining after a 15-min pulse/30-min chase (P = 0.01) and nearly twice as many phagosomes in vivo at 3 h (P = 0.009).
  • Aged *Klc1−/−* mice showed AMD-like changes: RPE autofluorescence was 545.2 ± 15 AU in WT vs. 778.9 ± 57.05 in mutant (P = 0.003); lipofuscin granule area was 5.5 ± 0.3% in controls vs. 7.1 ± 0.5% in mutant (P = 0.003); Bruch’s membrane was thicker at 17–18 mo (P = 0.0005) and 21–22 mo (P = 0.003), with basal laminar deposits and membranous debris. C3 immunolabeling increased in intensity (P = 0.02) and width (P = 0.005), with central/middle retinal increases (P = 0.02 and P = 0.002), plus MDA and C5b-9 immunoreactivity in mutant RPE/choroid.

Methods

  • Primary mouse RPE cultures and in vivo mouse retinas were used, comparing *Klc1−/−* mice with WT littermates; assays included POS phagocytosis and pulse-chase degradation, live-cell spinning-disk confocal tracking of labeled POS phagosomes, immunofluorescence, STED microscopy, EM/immunoEM, and Western blot.
  • Phagosome tracking used 3-min tracks with net displacement ≥2 µm and diameter 0.8–1.4 µm; measured segmental speed, run length, reversals, and net displacement, with Mann–Whitney or paired t tests.
  • In vivo analyses used mice on a 12-h light/dark cycle, retinas fixed at light onset or 3 h after, phagosome counts per RPE length, EM for Bruch’s membrane/lipofuscin/deposits, and fluorescence for autofluorescence, C3, MDA, and C5b-9, including aged 18–20-mo animals.

Limitations

  • Stated in the paper: *Klc1−/−* mice over 1 yr old typically developed cataracts, preventing rigorous fundus imaging, optical coherence tomography, and electroretinogram studies; basal linear deposits were not detected, which the authors attribute to the mouse retina lacking a fovea.
  • Evident from the text: the AMD-like phenotype is based mainly on microscopy in a mouse model and does not reproduce all human AMD features, such as foveal basal linear deposits, so the model is partial and functional visual consequences were not directly assessed.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1083/jcb.201410112

Cites

94 of 94 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 85 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The majority of apical-basal microtubules in mouse RPE are oriented with their plus ends more basal.

    “An enrichment of EB1 labeling, which is concentrated at the plus ends of microtubules, was detected in the more basal region (Fig. 1 C), indicating that the majority of these apical-basal microtubules were oriented with their plus ends more basal.”
    Quote in the paperSubstantial claim
  • Findingown data

    POS phagosomes move bidirectionally along microtubules in RPE cells.

    “and move bidirectionally along microtubules in retinal pigment epithelium cells”
    • Also stated in: § POS phagosomes move along microtubules in RPE cells · hedged
      “Motility along the labeled microtubules was evident as bidirectional movements, indicating the involvement of both plus and minus end–directed motors.”
    • Also stated in: § Discussion · boosted
      “By live-cell imaging, we have shown that POS phagosomes move bidirectionally along microtubules in RPE cells.”
    Quote in the paperSubstantial claim
  • Findingown data

    In EM of RPE with tubulin hooks, 92 of 129 microtubules in the basal half were decorated with hooks indicating basal projection of their plus ends.

    “in 20 separate images from the basal half of the cell body, 92 out of 129 microtubules were decorated with hooks that indicated basal projection of their plus ends.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Lack of KLC1 results in impaired POS phagosome degradation in RPE cells.

    “lack of KLC1 results in impaired POS phagosome motility and degradation”
    • Also stated in: § Degradation of POS phagosomes in Klc1−/− RPE cells · plain
      “there were many more ingested POS remaining in Klc1−/− than WT RPE”
    Quote in the paperSubstantial claim
  • Findingown data

    POS phagosomes associate with KLC1 in RPE cells.

    “Photoreceptor outer segment (POS) phagosomes associate with the kinesin light chain 1 (KLC1)”
    • Also stated in: § Association of MYO7A and KLC1 with POS phagosomes in RPE cells · plain
      “MYO7A, the heavy chain of kinesin-1, and KLC1, a light chain of kinesin-1 (tetrameric conventional kinesin, containing two motor subunits and two light chains), were observed to colocalize with some of the POS phagosomes”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 52
  • May combine two claims. 40
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    PARD3 labeling of basal bodies, evident in the same plane as the horizontal microtubules, was detected in 66% of primary mouse RPE cells.

    “PARD3 labeling of basal bodies, evident in the same plane as the horizontal microtubules (Fig. S1, E–G), was detected in 66% of the cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In retinal sections from mouse eyes fixed at light onset, MYO7A is detected primarily in the apical RPE, where it colocalizes with mAb1D4-labeled phagosomes.

    “In retinal sections from mouse eyes fixed at light onset, MYO7A was detected primarily in the apical RPE, where it colocalized with mAb1D4-labeled phagosomes”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The largest movements of POS phagosomes in WT RPE were in the x and y axes, indicating movement mainly along laterally oriented microtubules.

    “Tracks showed that the largest movements recorded were in the x and y axes (Fig. S2), indicating movement mainly along the microtubules oriented laterally.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Phagosomes in the apical region are associated more with MYO7A than KLC1, whereas phagosomes in the cell body are associated more with KLC1 than MYO7A.

    “phagosomes in the apical region (identified by phalloidin-TRITC labeling) were associated more with MYO7A than KLC1, whereas those in the cell body associated more with KLC1 than MYO7A”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    A primary cilium projects into the actin domain of each RPE cell.

    “a primary cilium could be observed projecting into the actin domain of each cell”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    When primary mouse RPE cells are incubated with purified POSs, the POSs bind to the apical surface and become ingested by phagocytosis.

    “When primary mouse RPE cells are incubated with purified POSs, the POSs bind to the apical surface of the RPE cells, and then become ingested by phagocytosis”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MYO7A is associated with 87 ± 3% of mAb1D4-labeled phagosomes, whereas KLC1 is associated with only 12 ± 2% of mAb1D4-labeled phagosomes.

    “MYO7A was associated with 87 ± 3% of mAb1D4-labeled phagosomes, whereas KLC1 was associated with only 12 ± 2% of mAb1D4-labeled phagosomes (n = 10 for each; ±SEM).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Segmental velocities of POS phagosomes covered a range of velocities that extended beyond 1 μm/s.

    “The segmental velocities of POS phagosomes (defined as the mean velocity of each continuous run, which is a movement without pausing or changing direction by >135°) covered a range of velocities that extended beyond 1 µm/s.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    In the center of the RPE cell, many lateral microtubules appear to emerge from the centrosome, but closer to the plasma membrane they are not associated with it.

    “In the center of the cell, many of the lateral microtubules appeared to emerge from the centrosome, but, closer to the plasma membrane, they were not associated with it”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    PARD3 or centrin labeling indicates centrosomes in the apical part of the microtubule domain of some RPE cells.

    “Labeling by PARD3 or centrin antibodies indicated centrosomes in the apical part of the microtubule domain of some cells”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Lateral microtubules appear responsible for much of the nonbasal EB1 labeling, which appears greater near the lateral plasma membrane.

    “These microtubules appear to be responsible for much of the nonbasal EB1 labeling, which appeared greater near the lateral plasma membrane”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The numbers of POSs bound to the apical surface at any time and the numbers of POSs ingested at the start of the chase period are comparable in Klc1−/− and WT RPE cells.

    “The numbers of POSs bound to the apical surface, at any time, and the numbers of POSs ingested at the start of the “chase” period were both comparable in mutant and WT cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In WT RPE, net displacement of phagosomes during 3-min tracks had a bias toward the plus end, but in Klc1−/− RPE there was no significant difference between the number of phagosomes displaced toward plus ends or minus ends from the starting point.

    “In WT RPE, the net displacement of phagosomes during the 3-min tracks had a bias toward the plus end, but, in mutant RPE, there was no significant difference between the number of phagosomes that were displaced toward the microtubule plus ends or toward the minus ends from the starting point”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Immunolabeling with antibodies against elastin and collagen IV shows no significant difference between Klc1−/− and control, suggesting that these regions of Bruch's membrane are relatively unaffected.

    “Immunolabeling with antibodies against elastin and collagen IV, which are present in the elastin layer and choroidal basement membrane of Bruch’s membrane, respectively (Marshall et al., 1992), showed no significant difference between mutant and control, suggesting that these regions of Bruch’s membrane were relatively unaffected.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Marshall et al., 1992 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    In mouse RPE, some lateral microtubules emerge from an apical centrosome, but other lateral microtubules in the periphery and vertical microtubules were not associated with a centrosome.

    “Here, we observed some lateral microtubules emerging from an apical centrosome, but other lateral microtubules in the periphery of the cell, as well as the vertical microtubules, were not associated with a centrosome.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mean segmental velocities of POS phagosomes in WT and Klc1−/− RPE are comparable in both plus and minus end directions, indicating that absence of KLC1 has no significant effect on velocity.

    “The mean segmental velocities in WT and Klc1−/− RPE were comparable in both plus and minus end directions (Fig. 4, D and E), indicating that the absence of KLC1 has no significant effect on velocity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The digestion rate of phagosomes in Kif3aflox/flox RPE cells treated with LV-Cre is not different from that in control cells, indicating that heterotrimeric kinesin-2 is not required.

    “The digestion rate of phagosomes in Kif3aflox/flox RPE cells that were treated with LV-Cre was not different from that in control cells (not depicted), indicating that heterotrimeric kinesin-2 was not required.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    MDA immunoreactivity was increased in the RPE of 18-mo-old Klc1−/− mice.

    “An increase in MDA immunoreactivity was observed in the RPE of Klc1−/− mice (Fig. 8, A and B).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The microtubule organization in the mouse RPE differed somewhat from that reported for β- and γ-tubulin labeling of chicken RPE.

    “The microtubule organization in the mouse RPE differed somewhat from that reported for β- and γ-tubulin labeling of chicken RPE, where it was suggested that the microtubules are directed basally and laterally from an apical centrosome (Rizzolo and Joshi, 1993).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rizzolo and Joshi, 1993

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    KLC1 is important in regulating phagosome bidirectionality; mean run length was decreased and reversal frequency was increased in Klc1−/− RPE cells.

    “On the other hand, KLC1 was found to be important in regulating phagosome bidirectionality; our tracking data showed that mean run length was decreased and reversal frequency was increased in Klc1−/− RPE cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Lack of KLC1 had no detectable effect on the ability of phagosomes to move along microtubules; segmental speed in Klc1−/− RPE was not significantly different from that in WT RPE.

    “The lack of KLC1, although important with respect to POS phagosome degradation and long-term retinal health, had no detectable effect on the ability of the phagosomes to move along microtubules; segmental speed in Klc1−/− RPE was not significantly different from that in WT RPE.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    MYO7A is associated with early phagosomes, whereas KLC1 is associated more with later-stage phagosomes.

    “Taking both RHO immunolabeling and subcellular location as indicators of POS phagosome maturity, our results show that MYO7A is associated with early phagosomes, whereas KLC1 is associated more with later-stage phagosomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Klc1−/− mouse manifests slowed POS phagosome degradation, coupled with subsequent increased autofluorescence, lipofuscin granules, and basal laminar deposits.

    “In this study, we found not only that the Klc1−/− mouse manifests slowed POS phagosome degradation, coupled with subsequent increased autofluorescence, lipofuscin granules, and basal laminar deposits, but we also observed the presence of other characteristic AMD phenotypes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The Klc1−/− RPE was associated with increased oxidative stress and activation of the complement pathway.

    “Second, we found that the Klc1−/− RPE was associated with increased oxidative stress and activation of the complement pathway (Fig. 8), two other hallmarks of AMD (Anderson et al., 2010; Weismann et al., 2011).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    No abnormal accumulation of oxidized material or complement proteins was observed in younger Klc1−/− mice, even though their retinas showed abnormal phagosome localization and degradation.

    “We did not observe any abnormal accumulation of oxidized material or complement proteins in younger Klc1−/− mice, even though sections of their retinas showed that they exhibited abnormal phagosome localization and degradation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In some Klc1−/− retinas, structures resembling drusen and invasion of the RPE and photoreceptor layers by neovascularization were observed.

    “Beyond oxidative stress and complement dysregulation, we also observed, in some Klc1−/− retinas, the presence of structures resembling drusen and the invasion of the RPE and photoreceptor layers by neovascularization (Fig. S3).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Myosin-7a is a functional actin motor.

    “Myosin-7a has been demonstrated to be a functional actin motor (Udovichenko et al., 2002)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Udovichenko et al., 2002 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    RPE cells phagocytose the distal disks of photoreceptor outer segments.

    “The event begins with phagocytosis of the distal disks by the RPE (Young and Bok, 1969).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Young and Bok, 1969

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In mice lacking myosin-7a, phagosome progression out of the actin-rich apical region is retarded.

    “In studies on mice lacking myosin-7a, it was shown that phagosome progression out of the actin-rich apical region was retarded (Gibbs et al., 2003).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gibbs et al., 2003

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Myosin-5 is involved in regulating the movement of phagocytosed beads from the periphery.

    “The unconventional myosin, myosin-5, was also found to be involved in regulating the movement of the phagocytosed beads from the periphery (Al-Haddad et al., 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Al-Haddad et al., 2001 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In mammals, approximately 10% of photoreceptor outer segment disks are replaced each day.

    “and (in mammals) ∼10% of the disks are replaced each day (Young, 1967)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Young, 1967 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In humans, myosin-7a is encoded by the gene defective in Usher syndrome 1B.

    “in humans, it is encoded by the gene that is defective in Usher syndrome 1B, a deaf-blindness disorder (Weil et al., 1995)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Weil et al., 1995 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In Tetrahymena thermophilia, Myo-1 is required for directed motility of latex-bead phagosomes.

    “In Tetrahymena thermophilia, a myosin, Myo-1, is required for the directed motility of latex-bead phagosomes (Hosein et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hosein et al., 2005 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the central mouse retina, each RPE cell serves over 200 photoreceptor cells.

    “in the central mouse retina, each RPE cell serves over 200 photoreceptor cells (Volland et al., 2015)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Volland et al., 2015 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    POS disk phagocytosis is triggered according to a daily cycle at the beginning of the light phase.

    “POS disk phagocytosis is triggered according to a daily cycle at the beginning of the light phase (LaVail, 1976)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites LaVail, 1976 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Microtubules and associated motors are required for transport of latex bead phagosomes from the cell periphery to the central region in macrophages.

    “Microtubules and associated motors were found to be required for transport of the beads from the cell periphery to the central region (Blocker et al., 1996, 1997, 1998).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Blocker et al., 1996, 1997, 1998

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Ingested POS phagosomes migrate from the apical region into the RPE cell and are degraded.

    “The ingested POS phagosomes then migrate from the apical region into the cell and are degraded (Gibbs et al., 2003), mimicking events that occur in vivo (LaVail, 1976; Herman and Steinberg, 1982).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Gibbs et al., 2003

      Not checked in the free run.

    • cites LaVail, 1976 source

      Not checked in the free run.

    • cites Herman and Steinberg, 1982

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The apical versus cell body association of MYO7A and KLC1 with phagosomes was obtained regardless of whether phagosomes were prelabeled or labeled with RHO antibodies, whether cells were albino or pigmented, and whether cells were single- or double-labeled.

    “This result was obtained regardless of whether phagosomes were from prelabeled POSs or labeled with RHO antibodies, whether the cells were albino or pigmented, and whether the cells were single- or double-labeled with MYO7A and KLC1 antibodies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    RPE cell lines lack some RPE polarity features, have reduced expression of a large proportion of RPE signature genes, and typically exhibit much slower phagosome degradation kinetics than primary RPE cultures.

    “cultures of RPE cell lines, which have been reported to lack some RPE polarity features (Lehmann et al., 2014), have reduced expression of a large proportion of “RPE signature genes” (Strunnikova et al., 2010), and typically exhibit kinetics of phagosome degradation that is much slower than that found in vivo and in primary RPE cultures (Finnemann et al., 2002; Mazzoni et al., 2014).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Lehmann et al., 2014 source

      Not checked in the free run.

    • cites Strunnikova et al., 2010 source

      Not checked in the free run.

    • cites Finnemann et al., 2002 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    MYO7A associates primarily with early phagosomes in the apical actin domain, and once phagosomes are delivered to the cell body region they associate with microtubule motors.

    “Collectively, these findings indicate that MYO7A associates primarily with early phagosomes in the apical actin domain, and that once they are delivered to the cell body region, they associate with microtubule motors.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Rat RPE cells lose their cilia during the first postnatal weeks.

    “It has been reported that rat RPE cells lose their cilia during the first postnatal weeks (Nishiyama et al., 2002).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Nishiyama et al., 2002 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Phagosome motility along lateral microtubules may be important for encounters with endosomes and lysosomes in the apical part of the cell body, and basal migration of phagosomes is necessary for phagosomes to be exposed to the entire population of CTSD-positive endosomes and lysosomes.

    “This observation suggests that phagosome motility along the lateral microtubules may be important for encounters with endosomes and lysosomes in the apical part of the cell body, and that the basal migration of phagosomes is necessary for phagosomes to be exposed to the entire population of CTSD-positive endosomes and lysosomes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The distribution of CTSD-positive endosomes and lysosomes in fixed retinal sections reflects their distribution in live RPE cells.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The microtubule organization observed in mouse RPE compares more closely to that reported for other confluent epithelial cells.

    “In this respect, the microtubule organization observed here compares more closely to that reported for other confluent epithelial cells (Bacallao et al., 1989; Gilbert et al., 1991).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Bacallao et al., 1989 source

      Not checked in the free run.

    • cites Gilbert et al., 1991 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies of neuronal vesicles and endosomes support the tug-of-war model.

    “Support for this model includes studies of neuronal vesicles (Hendricks et al., 2010) and endosomes (Soppina et al., 2009).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hendricks et al., 2010 source

      Not checked in the free run.

    • cites Soppina et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In the RPE, the delivery of POS phagosomes appears to involve a cooperative relay, with myosin-7a transport of early phagosomes through the apical actin filament network, followed by microtubule motor transport of more mature phagosomes in the cell body.

    “Therefore, in the RPE, the delivery of POS phagosomes appears to involve a cooperative relay, with myosin-7a transport of early phagosomes through the apical actin filament network, followed by microtubule motor transport of more mature phagosomes in the cell body, where the CTSD-containing endosomes and lysosomes are located.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Different models have been proposed to explain how kinesin-1 and dynein might be regulated to generate bidirectional transport.

    “Different models have been proposed to explain how kinesin-1 and dynein might be regulated to generate bidirectional transport (Fu and Holzbaur, 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fu and Holzbaur, 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The movement of latex-bead phagosomes to microtubule motors appeared to be inhibited by association with myosin-5a in macrophages.

    “The movement of latex-bead phagosomes to microtubule motors appeared to be inhibited by association with myosin-5a in macrophages (Al-Haddad et al., 2001).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Al-Haddad et al., 2001 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    To achieve bidirectional movements, kinesin-1 is presumably paired with dynein.

    “To achieve the bidirectional movements, kinesin-1 is presumably paired with dynein.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies have shown cargoes that maintain a stable population of associated motors when changing direction or pausing, suggesting regulation of motor activity rather than relative changes in motor association.

    “Recently, however, studies have shown cargoes that maintain a stable population of associated motors when changing direction, or even pausing, suggesting regulation of motor activity rather than relative changes in motor association (Encalada et al., 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Encalada et al., 2011 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Myosin-5a and myosin-7a have comparable roles in the motility of melanosomes; both capture melanosomes from microtubule transport.

    “Myosin-5a and myosin-7a have comparable roles in the motility of melanosomes; both capture melanosomes from microtubule transport: myosin-5a in melanocytes (Wu et al., 1998) and myosin-7a in RPE cells (Gibbs et al., 2004; Lopes et al., 2007).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Wu et al., 1998

      Not checked in the free run.

    • cites Gibbs et al., 2004 source

      Not checked in the free run.

    • cites Lopes et al., 2007 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Loss of cilia in adult RPE is an artifact introduced if the neural retina is removed from the RPE.

    “consistent with a recent study that suggests loss of cilia in adult RPE is an artifact that is introduced if the neural retina is removed from the RPE (Lehmann et al., 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lehmann et al., 2014 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bidirectional movements have been reported for a variety of organelles and vesicles, including mitochondria, autophagosomes, and vesicles during axonal transport.

    “Bidirectional movements have been reported for a variety of organelles and vesicles (Welte, 2004), including even those that move persistently in one direction, such as mitochondria (Saxton and Hollenbeck, 2012), autophagosomes (Maday et al., 2012), and vesicles (Encalada et al., 2011), as they undergo axonal transport.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Welte, 2004 source

      Not checked in the free run.

    • cites Saxton and Hollenbeck, 2012

      Not checked in the free run.

    • cites Maday et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In one model, direction of travel is the outcome of a tug of war between the opposing motors associated with the cargo, and a change in direction is effected by a change in the relative number of engaged kinesin-1 and dynein molecules.

    “In one model, direction of travel is the outcome of a tug of war between the opposing motors associated with the cargo. A change in direction is effected by a change in the relative number of engaged kinesin-1 and dynein molecules (Welte, 2004; Müller et al., 2008).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Welte, 2004 source

      Not checked in the free run.

    • cites Müller et al., 2008 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    KLC1 is predominant in neuronal tissues.

    “KLC1 is predominant in neuronal tissues (Rahman et al., 1998).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rahman et al., 1998 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Kinesin light chains have been proposed to function in either cargo binding or modulation of motor activity.

    “Kinesin light chains have been proposed to function in either cargo binding or modulation of motor activity (Pernigo et al., 2013; Fu and Holzbaur, 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Pernigo et al., 2013 source

      Not checked in the free run.

    • cites Fu and Holzbaur, 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In Drosophila, interactions between KLC and dynein intermediate chain are important in the switch between plus and minus end-directed movement.

    “Similar results have been found in a study of kinesin-1 transport of amyloid precursor protein along axons in Drosophila; in this study, it appeared that interactions between KLC and dynein intermediate chain are important in the switch between plus and minus end–directed movement (Reis et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Reis et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    JIP1 is an important coordinator of kinesin and dynein motors in the regulation of directionality; it binds KLC and KHC, as well as the dynein-dynactin complex.

    “In addition, an important coordinator of kinesin and dynein motors in the regulation of directionality is the motor-scaffolding protein, JIP1 (c-Jun N-terminal kinase–interacting protein 1), which binds KLC and KHC, as well as the dynein–dynactin complex (Verhey et al., 2001; Fu and Holzbaur, 2013).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Verhey et al., 2001 source

      Not checked in the free run.

    • cites Fu and Holzbaur, 2013

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The movement of phagosomes along microtubules likely facilitates the interaction of phagosomes with endosomes and lysosomes.

    “Earlier studies on the phagocytosis of latex beads by macrophages concluded that the movement of the phagosomes along microtubules likely facilitates the interaction of phagosomes with endosomes and lysosomes (Rabinowitz et al., 1992; Desjardins et al., 1994).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Rabinowitz et al., 1992 source

      Not checked in the free run.

    • cites Desjardins et al., 1994 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A portion of POS phagosomes becomes decorated by LC3 and converges on the autophagic pathway.

    “Recent studies have shown that a portion of POS phagosomes becomes decorated by LC3 and converges on the autophagic pathway (Kim et al., 2013; Frost et al., 2014), suggesting the possibility of comparable regulation for some of the POS phagosomes.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Kim et al., 2013 source

      Not checked in the free run.

    • cites Frost et al., 2014 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In the transport of autophagosomes along axons, LC3 on the surface of the autophagosomes binds to JIP1 and thus influences directionality.

    “In the transport of autophagosomes along axons, LC3, on the surface of the autophagosomes, binds to JIP1 and thus influences directionality (Fu et al., 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fu et al., 2014

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Inefficiencies in POS phagosome degradation promote an increased accumulation of lipofuscin and sub-RPE deposits, leading to RPE pathogenesis and age-related visual impairment, as in AMD.

    “For decades, it has been proposed that inefficiencies in POS phagosome degradation promote an increased accumulation of lipofuscin and sub-RPE deposits, leading to RPE pathogenesis and age-related visual impairment, as in AMD (Hogan, 1972; Feeney, 1973; Feeney-Burns and Eldred, 1983; Sparrow and Boulton, 2005; Sparrow et al., 2012; Bowes Rickman et al., 2013).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Hogan, 1972

      Not checked in the free run.

    • cites Feeney, 1973

      Not checked in the free run.

    • cites Feeney-Burns and Eldred, 1983

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    REP1 facilitates isoprenyl modifications of RAB GTPases and is encoded by the CHM gene, which is mutant in the retinal degeneration choroideremia.

    “REP1 facilitates isoprenyl modifications of RAB GTPases and is encoded by the CHM gene, which is mutant in the retinal degeneration choroideremia (Seabra et al., 1993).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Seabra et al., 1993 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the mutant CTSD transgenic mouse, sub-RPE deposits and photoreceptor degeneration were observed.

    “In the mutant CTSD transgenic mouse, sub-RPE deposits and photoreceptor degeneration were observed (Rakoczy et al., 2002), and in a conditional Chm−/− mouse, abnormally high accumulation of lipofuscin and sub-RPE deposits were also reported (Wavre-Shapton et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rakoczy et al., 2002 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The present observations are more consistent with a role in which KLC1 modulates the switching between kinesin-1 and dynein motor activity, affecting the whole motor complex including dynein and KHC.

    “However, the present observations are more consistent with a role in which KLC1 modulates the switching between kinesin-1 and dynein motor activity, and thus potentially a role that affects the whole motor complex, including dynein as well as KHC.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    KLC1 has been shown previously to promote autoinhibition of KHC.

    “KLC1 has been shown previously to promote autoinhibition of KHC (Verhey et al., 1998; Friedman and Vale, 1999).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Verhey et al., 1998 source

      Not checked in the free run.

    • cites Friedman and Vale, 1999

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    These findings point to a regulatory function for KLC1, rather than essential linkage of POS phagosomes to kinesin transport.

    “These findings point to a regulatory function for KLC1, rather than essential linkage of POS phagosomes to kinesin transport.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    CTSD is abundant in RPE lysosomes and is a major contributor to rhodopsin proteolysis.

    “CTSD is abundant in RPE lysosomes and is a major contributor to rhodopsin proteolysis (Regan et al., 1980), so that inhibited phagosome degradation appears to be the primary defect in the CTSD mouse.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Regan et al., 1980 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Studies of axonal transport of vesicles containing prion protein have shown that KLC1 is required for normal retrograde transport activity.

    “Studies of the axonal transport of vesicles containing prion protein have shown that KLC1 is also required for normal retrograde transport activity (Encalada et al., 2011).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Encalada et al., 2011 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Data on phagosome trajectories were obtained from three WT and three Klc1−/− independent RPE primary cultures.

    “Data were obtained from three WT and three Klc1−/− independent RPE primary cultures, grown in coverglass chambers.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All constructs were sequenced to confirm identity before use.

    “All constructs were sequenced to confirm identity before use.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Bound and ingested POSs were identified and distinguished from each other as described previously.

    “Bound and ingested POSs were identified and distinguished from each other, as described previously (Gibbs et al., 2003).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gibbs et al., 2003

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Myo7a mutant RPE, a delay in clearance of phagosomes from the actin-rich apical RPE has been detected, but no delay in phagosome degradation detectable in vivo, and Myo7a mutant mice do not undergo detectable RPE pathogenesis.

    “A delay in the clearance of phagosomes from the actin-rich, apical RPE has been detected in Myo7a mutant RPE, but unlike that observed here with Klc1−/− mice, there was no delay in phagosome degradation detectable in vivo (Gibbs et al., 2003), and Myo7a mutant mice do not undergo detectable RPE pathogenesis (Williams, 2008).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Gibbs et al., 2003

      Not checked in the free run.

    • cites Williams, 2008 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Excessive amounts of neutral lipids accumulate under the Klc1−/− RPE, and this characteristic is a major aspect of AMD.

    “Therefore, it appears that excessive amounts of neutral lipids accumulate under the Klc1−/− RPE, and this characteristic is a major aspect of AMD (Pikuleva and Curcio, 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Pikuleva and Curcio, 2014

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    OTAP secondary fixation was originally used to preserve lipid droplets in atherosclerosis, with paraphenylenediamine preserving osmium-treated neutral lipids such as cholesterol and apolipoproteins.

    “OTAP secondary fixation was originally used to preserve lipid droplets in atherosclerosis (Guyton and Klemp, 1988), with the paraphenylenediamine preserving osmium-treated neutral lipids, such as cholesterol and apolipoproteins.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Guyton and Klemp, 1988

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Homozygous mutants were distinguished from WT controls by genotyping.

    “Homozygous mutants were distinguished from the WT controls by genotyping, as described previously (Rahman et al., 1999).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rahman et al., 1999 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oxidative stress adducts and components of the complement system accumulate in drusen and sub-RPE deposits of patients with AMD.

    “Oxidative stress adducts and components of the complement system have been found to accumulate in drusen and sub-RPE deposits of patients with AMD (Weismann et al., 2011; Shaw et al., 2012), and mice with mutations making them prone to oxidative stress or dysregulation of the complement pathway have been presented as models of AMD (Imamura et al., 2006; Justilien et al., 2007; Hollyfield et al., 2”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Weismann et al., 2011 source

      Not checked in the free run.

    • cites Shaw et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mutant CHM results in underprenylated RAB27A, which is the RAB that links myosin-7a to melanosomes.

    “Interestingly, mutant CHM results in underprenylated RAB27A (Seabra et al., 1995), which is the RAB that links myosin-7a to melanosomes (Futter et al., 2004; Gibbs et al., 2004).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Seabra et al., 1995 source

      Not checked in the free run.

    • cites Futter et al., 2004 source

      Not checked in the free run.

    • cites Gibbs et al., 2004 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All procedures conformed to institutional animal care and use authorizations.

    “All procedures conformed to institutional animal care and use authorizations.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Mice with mutations making them prone to oxidative stress or dysregulation of the complement pathway have been presented as models of AMD.

    “and mice with mutations making them prone to oxidative stress or dysregulation of the complement pathway have been presented as models of AMD (Imamura et al., 2006; Justilien et al., 2007; Hollyfield et al., 2008; Ufret-Vincenty et al., 2010).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Imamura et al., 2006 source

      Not checked in the free run.

    • cites Justilien et al., 2007 source

      Not checked in the free run.

    • cites Hollyfield et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The absence of basal linear deposits in Klc1−/− retina is to be expected, given that basal linear deposits form mostly in the fovea, a small central region of the macula that contains only cone photoreceptors, which is not present in a mouse retina.

    “This difference is to be expected, given that basal linear deposits form mostly in the fovea (Curcio et al., 2013), a small central region of the macula that contains only cone photoreceptors (Osterberg, 1935), which is not present in a mouse retina.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Curcio et al., 2013 source

      Not checked in the free run.

    • cites Osterberg, 1935

      Not checked in the free run.

    • Rests on an assumption: The fovea is not present in a mouse retina.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Sections from control or mutant mice were imaged under identical conditions.

    “Sections from control or mutant mice were imaged under identical conditions.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Sub-RPE deposits were quantified with sections representing at least four animals of each genotype (WT and mutant).

    “Sub-RPE deposits were quantified with sections representing at least four animals of each genotype (WT and mutant).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Phagosomes derived from outer segment shedding were identified by their characteristic structure (disk membrane presence).

    “Phagosomes derived from outer segment shedding were identified by their characteristic structure (disk membrane presence).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Microtubule decoration was performed according to a published procedure.

    “Microtubule decoration was performed according to a published procedure (Euteneuer and McIntosh, 1980; Troutt and Burnside, 1988).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Euteneuer and McIntosh, 1980

      Not checked in the free run.

    • cites Troutt and Burnside, 1988

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Hook curvature is directly related to microtubule polarity.

    “Hook curvature is directly related to microtubule polarity.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Euteneuer and McIntosh, 1980

      Not checked in the free run.

    • cites Troutt and Burnside, 1988

      Not checked in the free run.

85 of 85

  • The paper relies on this without support.

    The rate of phagosome degradation in the primary RPE cell culture system compares to that in vivo.

    “we have developed a primary RPE cell culture system in which the rate of phagosome degradation compares to that in vivo”

  • The paper relies on this without support.

    The orientation of lateral microtubules measured in cultured RPE cells reflects the orientation relevant for interpreting phagosome movement in the tracking experiments.

    “From regions that were used for phagosome tracking, we counted 89% of growing lateral microtubules (n = 130) oriented in this manner.”

  • The paper relies on this without support.

    The distribution of CTSD-positive endosomes and lysosomes in fixed retinal sections reflects their distribution in live RPE cells.

    “Immunolabeling of retinal sections showed that they were limited to the cell body (significant numbers were not detected in the apical domain)”

  • The paper relies on this without support.

    Oxidative stress and hyperactivation of the complement pathway are implicated in the pathogenesis of AMD.

    “Oxidative stress and hyperactivation of the complement pathway have been implicated in the pathogenesis of AMD.”

  • The paper relies on this without support.

    Neovascularization is characteristic of a late and severe stage in AMD, known as “wet” AMD.

    “The latter is characteristic of a late and severe stage in AMD, known as “wet” AMD.”

  • The paper relies on this without support.

    In humans, evidence of large drusen in fundus images is an indicator of early- and intermediate-stage AMD.

    “In humans, evidence of large drusen in fundus images is an indicator of early- and intermediate-stage AMD.”

  • The paper relies on this without support.

    The fovea is not present in a mouse retina.

    “which is not present in a mouse retina.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The rate of phagosome degradation is affected by motility along the RPE cell microtubules.

    “the rate of phagosome degradation is affected by motility along the RPE cell microtubules (Jiang et al., 2015)”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Jiang et al., 2015

  • Imaging of OS phagosomes in live primary RPE cells showed that the phagosomes undergo rapid back and forth movements along labeled microtubules.

    “Imaging of OS phagosomes in live primary RPE cells showed that the phagosomes undergo rapid back and forth movements along labeled microtubules (see Video 2 in Jiang et al., 2015).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Jiang et al., 2015

  • OS phagosomes associate with subunits of both kinesin-1 and cytoplasmic dynein-1, which are plus- and minus-end directed microtubule motors, respectively, consistent with bidirectional motility along microtubules.

    “Demonstrated association with subunits of both kinesin-1 (Jiang et al., 2015) and cytoplasmic dynein-1 (Esteve-Rudd et al., 2018), which are plus- and minus-end directed microtubule motors, respectively, is consistent with bidirectional motility along microtubules.”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Jiang et al., 2015

  • Some mutant retinas also showed structures resembling drusen, and neovascularization of the RPE and photoreceptor layers.

    “Some mutant retinas also showed structures resembling drusen, and neovascularization of the RPE and photoreceptor layers (Jiang et al., 2015).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Jiang et al., 2015

  • Both myosin-7a and myosin-6 have been reported to colocalize with OS phagosomes in the RPE.

    “Both myosin-7a and myosin-6 have been reported to colocalize with OS phagosomes in the RPE (Jiang et al., 2015; Yu et al., 2018).”

    From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Jiang et al., 2015

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Authors
Jiang, M., Esteve-Rudd, J., Lopes, V. S., Diemer, T., Lillo, C., Rump, A., & Williams, D. S.
Affiliations
  • University of California, Los Angeles (US)
  • Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, CA 90095 1
  • University of California San Diego (US)
Corresponding author
Williams, David S.
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2015-08-10
Volume
210
Issue
4
Pages
595-611
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.201410112
PMC
PMC4539993
OpenAlex
W2147481857
Semantic Scholar
3f2655a9bd427dbd7a080b4ceef43a3fb9301396
Cited by
85
References
94
Citations by year
2026: 4 · 2025: 4 · 2024: 9 · 2023: 10 · 2022: 14 · 2021: 4 · 2020: 12 · 2019: 8 · 2018: 10 · 2017: 7 · 2016: 2 · 2015: 1
FWCI
6.40
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
Funders
  • National Institutes of Health
  • National Eye Institute (EY13408, R01EY013408, EY-00331, R01EY007042, EY07042, P30EY000331)
  • California NanoSystems Institute
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
Keywords
retinal pigment epithelium, KLC1, microtubule motor proteins, photoreceptor outer segments, age-related macular degeneration, bidirectional transport, oxidative stress, inflammation
MeSH terms
Myosin VIIa, Animals, Biological Transport, Cells, Cultured, Complement Activation, Macular Degeneration, Mice, Inbred C57BL, Microtubule-Associated Proteins, Myosins, Phagosomes, Kinesins, Mice, Knockout, Oxidative Stress, Retinal Pigment Epithelium, Retinal Photoreceptor Cell Outer Segment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

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