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Cited by 609Microtubule and mitosis dynamicsProtein Kinase Regulation and GTPase SignalingCellular transport and secretion

Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules

Open access
Verhey, Kristen J., Meyer, Debra, Deehan, Reneé, Blenis, John, Schnapp, Bruce J., Rapoport, Tom A., Margolis, Ben·2001·The Journal of Cell Biology
DOI 10.1083/jcb.152.5.959PMC PMC2198804
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Abstract

The cargo that the molecular motor kinesin moves along microtubules has been elusive. We searched for binding partners of the COOH terminus of kinesin light chain, which contains tetratricopeptide repeat (TPR) motifs. Three proteins were found, the c-jun NH2-terminal kinase (JNK)–interacting proteins (JIPs) JIP-1, JIP-2, and JIP-3, which are scaffolding proteins for the JNK signaling pathway. Concentration of JIPs in nerve terminals requires kinesin, as evident from the analysis of JIP COOH-terminal mutants and dominant negative kinesin constructs. Coprecipitation experiments suggest that kinesin carries the JIP scaffolds preloaded with cytoplasmic (dual leucine zipper–bearing kinase) and transmembrane signaling molecules (the Reelin receptor, ApoER2). These results demonstrate a direct interaction between conventional kinesin and a cargo, indicate that motor proteins are linked to their membranous cargo via scaffolding proteins, and support a role for motor proteins in spatial regulation of signal transduction pathways.

AI snapshot

Written from the paper’s full text.

TL;DR

A yeast two-hybrid screen using the kinesin light chain (KLC) tetratricopeptide repeat (TPR) motifs identified JIP-1, JIP-2, and JIP-3 as direct binding partners, and disruption of this interaction mislocalizes JIPs in neuronal cells. The authors conclude that JIP scaffolding proteins are a cargo for conventional kinesin and that kinesin can carry a preassembled JIP signaling complex including DLK and ApoER2.

Key findings

  • The KLC TPR motifs bound JIP-1, JIP-2, and JIP-3; nine two-hybrid clones corresponded to overlapping fragments of these three cDNAs, and binding was confirmed by coimmunoprecipitation of tagged KLC and JIPs in COS/293 cells.
  • JIP-1 binding to KLC required the last 11 COOH-terminal amino acids, especially tyrosine at position −3 (Y709); JIP-1 (307–700) and JIP-1 (Y709A) failed to bind KLC, whereas JIP-1 (P704A) still bound.
  • JIP localization to neurite tips required kinesin: JIP-1 (307–700) and JIP-1 (Y709A) were mislocalized throughout cells, and dominant negative KLC TPRs or KLC heptad repeats mislocalized endogenous JIP-1; control PP5 TPRs and KHC-891 had no effect. Flag-tagged JIP-2 and JIP-3 tip localization was also abolished by the kinesin dominant negative.
  • Kinesin immunoprecipitates from rat brain high-speed supernatant coprecipitated JIP-1, DLK, and ApoER2, and MT binding in AMP-PNP also coprecipitated JIP-1, DLK, and ApoER2; MKK3, TrkA, and type I sodium channel were not coprecipitated. Dominant negative KLC TPRs also mislocalized endogenous DLK.

Methods

  • Yeast two-hybrid screen of a mouse brain cDNA library using KLC TPR motifs as bait in PJ69-4A cells, with PP5 TPRs and GAL4 DNA-binding domain as controls.
  • Coimmunoprecipitation in COS and HEK293 cells using HA-, Myc-, and Flag-tagged KLC, JIP, and JIP-1 mutant constructs; immunofluorescence in differentiated N1E 115 and CAD neuronal cells to score JIP localization.
  • Rat brain high-speed supernatant immunoprecipitation with anti-KHC mAb H2 and microtubule-binding assays with ATP or AMP-PNP, followed by immunoblotting for KHC, JIP-1, DLK, ApoER2, MKK3, TrkA, and type I sodium channel.

Limitations

  • The paper states that effects of kinesin dominant negatives on endogenous JIP-2 or JIP-3 were not tested due to lack of appropriate reagents, and that ApoER2 antibodies were not suitable for localization experiments.
  • The paper states that further experiments are required to determine whether JIP binding is necessary and sufficient for kinesin motor activation and whether known signal transduction pathways regulate kinesin activity.
  • Evident from the text: much of the interaction and localization evidence relies on overexpression, tagged constructs, and dominant negative fragments in cultured cells, and the model that kinesin carries a vesicle-associated JIP complex is proposed but not directly imaged or shown with endogenous vesicle transport.

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

Integrity signals

Registry

Crossref · 10.1083/jcb.152.5.959

Cites

89 of 89 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 36 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    The interaction between KLC and JIP-1 requires the last 11 amino acids of JIP-1 and, in particular, the tyrosine residue at position −3 from the end.

    “These data demonstrate that the interaction between KLC and JIP-1 requires the last 11 amino acids of JIP-1 and, in particular, the tyrosine residue at position −3 from the end.”
    • Also stated in: § The JIP-1 COOH-terminal Residues Are Required for Binding to the KLC TPR Motifs · plain
      “In contrast, no coprecipitation of the JIP-1 construct missing the COOH-terminal 11 residues, JIP-1 (307–700), or the tyrosine to alanine mutant, JIP-1 (Y709A), was observed (Fig. 3 C).”
    Quote in the paperSubstantial claim
  • Findingown data

    A yeast two-hybrid screen using the TPR motifs of kinesin light chain (KLC) as bait identified JIP-1, JIP-2, and JIP-3 as interacting proteins.

    “Three proteins were found, the c-jun NH2-terminal kinase (JNK)–interacting proteins (JIPs) JIP-1, JIP-2, and JIP-3, which are scaffolding proteins for the JNK signaling pathway.”
    • Also stated in: § Direct Interaction of KLC and the JIP Proteins · plain
      “Nine of the clones isolated correspond to overlapping fragments of three different cDNAs encoding JIP-1, JIP-2, and JIP-3 (Fig. 1 B).”
    Quote in the paperSubstantial claim
  • Findingown data

    The TPR motifs of KLC directly interact with the JIP proteins.

    “These data confirm a direct interaction between the TPR motifs of KLC and the JIP proteins.”
    • Also stated in: § Direct Interaction of KLC and the JIP Proteins · plain
      “Using anti-Flag antibodies, precipitation of JIP-1, JIP-2, or JIP-3 resulted in coprecipitation of HA-tagged full-length KLC (Fig. 2, lanes 2, 5, and 8).”
    Quote in the paperSubstantial claim
  • Findingown data

    Precipitation of kinesins by binding to MTs in the presence of AMP-PNP also resulted in the coprecipitation of ApoER2.

    “precipitation of kinesins by binding to MTs in the presence of AMP-PNP also resulted in the coprecipitation of ApoER2.”
    Quote in the paperSubstantial claim
  • Findingown data

    Expression of the HA-tagged TPR motifs of KLC in differentiated CAD cells causes endogenous JIP-1 protein to shift from the tips of neuronal processes to throughout the entire cell.

    “Indeed, expression of the HA-tagged TPR motifs of KLC in differentiated CAD cells caused the localization of endogenous JIP-1 protein to shift from the tips of the neuronal processes (Fig. 5 A, arrows indicate untransfected cells) to throughout the entire cell (Fig. 5 A, arrowheads indicate transfected cells).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Expression of the KLC TPR motifs acts as a dominant negative by binding kinesin cargo and preventing its transport because the construct lacks an attached motor domain.
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 14

  • May combine two claims.

    Findingown data

    Immunoprecipitation of the HA-tagged TPR motifs of KLC coprecipitated JIP-1 (307-711) and the JIP-1 (P704A) point mutant, but not the JIP-1 (307-700) deletion mutant or the JIP-1 (Y709A) point mutant.

    “Immunoprecipitation of the HA-tagged TPR motifs of KLC coprecipitated the NH2-terminal truncation JIP-1 (307–711), which contains the wild-type tail sequences (Fig. 3 C); this is consistent with the results of the two-hybrid screen where all of the positive JIP-1 and JIP-2 clones encode the extreme COOH termini of the proteins (Fig. 1 B).”
    • Also stated in: § The JIP-1 COOH-terminal Residues Are Required for Binding to the KLC TPR Motifs · plain
      “Immunoprecipitation of the HA-tagged TPR motifs of KLC also coprecipitated the proline to alanine point mutant, JIP-1 (P704A) (Fig. 3 C). In contrast, no coprecipitation of the JIP-1 construct missing the COOH-terminal 11 residues, JIP-1 (307–700), or the tyrosine to alanine mutant, JIP-1 (Y709A), was observed (Fig. 3 C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The extreme COOH-terminal sequences of JIP-1 and JIP-2 (PTEDIYLE) are identical and are completely conserved across species.

    “Interestingly, the extreme COOH-terminal sequences of JIP-1 and JIP-2 (PTEDIYLE) are identical and are completely conserved across species (Fig. 3 A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Full-length JIP-1 and the NH2-terminal truncation JIP-1 (307-711) localize to the tips of neurites in differentiated N1E 115 cells, and mutation of the proline residue JIP-1 (P704A) has no effect on JIP-1 localization.

    “As seen in Fig. 4B and Fig. C, full-length JIP-1 and the NH2-terminal truncation JIP-1 (307–711) localize to the tips of the neurites (arrowheads indicate tip staining) identical to the staining seen for endogenous JIP-1 (Fig. 5; Meyer et al. 1999; Yasuda et al. 1999; Kelkar et al. 2000; Pellet et al. 2000).”
    • Also stated in: § JIP-1 Is a Cargo for Kinesin · plain
      “Likewise, mutation of the proline residue, JIP-1 (P704A), had no effect on JIP-1 localization (Fig. 4 E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Flag-tagged JIP-2 and JIP-3 localize to the tips of neurites in differentiated CAD cells, and this localization is abolished by coexpression of the kinesin dominant negative construct.

    “However, when expressed at low levels in differentiated CAD cells, Flag-tagged JIP-2 and JIP-3 localize to the tips of the neurites (Fig. 6A and Fig. B, arrows indicate untransfected cells), and this localization is abolished by coexpression of the kinesin dominant negative construct (Fig. 6A and Fig. B, arrowheads indicate transfected cells).”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Expression of the KLC TPR motifs acts as a dominant negative by binding kinesin cargo and preventing its transport because the construct lacks an attached motor domain.

  • May combine two claims.

    Findingown data

    JIP-1 (307-700) and JIP-1 (Y709A) exhibit localization throughout the cell with no concentration at the neurite tips.

    “In contrast, JIP-1 with a deletion of the 11 COOH-terminal residues, JIP-1 (307–700), or mutation of the tyrosine residue, JIP-1 (Y709A), exhibited localization throughout the cell with no concentration at the neurite tips (Fig. 4D and Fig. F, arrows indicate staining of the cell body).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Expression of the dominant negative HA-tagged KLC TPRs has no effect on the localization of microtubules, neurofilaments, mitochondria, endoplasmic reticulum, Golgi complex, endosomes, lysosomes, actin, vimentin, or synaptophysin in cultured cells.

    “Importantly, in control experiments, expression of the dominant negative HA-tagged KLC TPRs had no effect on the localization of MTs in CAD cells (Fig. 6 C) or in a variety of other cell lines (data not shown), demonstrating that the effects on JIP localization are not due to a global effect on MT organization.”
    • Also stated in: § JIP-1 Is a Cargo for Kinesin · plain
      “In addition, expression of the HA-tagged KLC TPRs had no effect on the localization of neurofilaments (Fig. 6 D) or mitochondria (Fig. 6 E) in CAD cells, or on the localization of the endoplasmic reticulum, the Golgi complex, endosomes, lysosomes, actin, vimentin, or synaptophysin in a variety of cultured cell lines (data not shown).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Transmembrane proteins TrkA and the type I sodium channel were not coprecipitated with kinesin, although they were present in the high speed supernatant fraction.

    “the transmembrane proteins TrkA, a receptor for nerve growth factor, and the type I sodium channel were not coprecipitated (Fig. 7 A), although they were present in the high speed supernatant fraction.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Kinesin and JIPs are not necessary for axonal growth.

    “Kinesin and JIPs are not necessary for axonal growth because mislocalization of JIP-1 by dominant negative kinesin constructs does not prevent neurite outgrowth (Fig. 5)”
    Quote in the paperSubstantial claim

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

    Premisecitation

    KLC stabilizes the inhibitory interaction of the KHC COOH-terminal and motor domains.

    “KLC stabilizes the inhibitory interaction of the KHC COOH-terminal and motor domains (Verhey et al. 1998).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Verhey et al. 1998 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The JIP scaffolding proteins act not only as motor-cargo linkers but are integral components of the cargo as well.

    “These data support the assertion that JIP-2 and JIP-3 are also cargoes for kinesin and provide strong evidence that the JIP scaffolding proteins act not only as motor–cargo linkers but are integral components of the cargo as well.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    JIP-3 can form oligomeric complexes with itself and JIP-2 but has no sequence relationship to JIP-1 or JIP-2.

    “JIP-3 (also known as JSAP) can form oligomeric complexes with itself and JIP-2 but has no sequence relationship to JIP-1 or JIP-2 (Ito et al. 1999; Kelkar et al. 2000).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ito et al. 1999 source

      Not checked in the free run.

    • cites Kelkar et al. 2000 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Evidence linking kinesin directly to any of the proposed cellular roles is lacking; a molecular relationship between kinesin and a cargo has yet to be established.

    “However, evidence linking kinesin directly to any of the proposed cellular roles is lacking; that is, a molecular relationship between kinesin and a cargo has yet to be established.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    JIP-1 and JIP-2 are ∼50% identical, have a similar domain structure, and can form homodimeric and heterodimeric complexes.

    “JIP-1 (also known as IB1) and JIP-2 are ∼50% identical, have a similar domain structure, and can form homodimeric and heterodimeric complexes (Yasuda et al. 1999).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Yasuda et al. 1999 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    JIP-1 and JIP-2 interact with rhoGEF and with the cell surface receptor for Reelin, ApoER2.

    “JIP-1 and JIP-2 have additionally been found to interact with rhoGEF (Meyer et al. 1999) and with the cell surface receptor for Reelin, ApoER2 (Stockinger et al. 2000).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Meyer et al. 1999 source

      Not checked in the free run.

    • cites Stockinger et al. 2000 source

      Not checked in the free run.

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

    Premisecitation

    Several studies point to a role for the KHC COOH terminus in cargo binding, as this region binds membranes.

    “Several studies point to a role for the KHC COOH terminus in cargo binding, as this region binds membranes (Skoufias et al. 1994; Bi et al. 1997).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Skoufias et al. 1994 source

      Not checked in the free run.

    • cites Bi et al. 1997

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    JIP-2 and JIP-3 are also cargoes for kinesin.

    “These data support the assertion that JIP-2 and JIP-3 are also cargoes for kinesin and provide strong evidence that the JIP scaffolding proteins act not only as motor–cargo linkers but are integral components of the cargo as well.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    No homologue for kinectin exists in the Drosophila genome, arguing against its role in kinesin-driven transport.

    “No homologue for kinectin exists in the Drosophila genome, arguing against its role in kinesin-driven transport (Goldstein and Gunawardena 2000).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Goldstein and Gunawardena 2000

      Not checked in the free run.

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

    Premisecitation

    JIP proteins bind simultaneously to the three components of the JNK signaling pathway: the MAP kinase kinase kinase (DLK, MLK3, and others), the MAP kinase kinase (MKK4 and MKK7), and the MAP kinase JNK.

    “They bind simultaneously to the three components of the JNK signaling pathway, the MAP kinase kinase kinase (DLK, MLK3, and others), the MAP kinase kinase (MKK4 and MKK7), and the MAP kinase JNK (for reviews see Davis 2000; Mielke and Herdegen 2000).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Davis 2000 source

      Not checked in the free run.

    • cites Mielke and Herdegen 2000

      Not checked in the free run.

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

    Premisecitation

    In the TPR-containing proteins Hop and PAS8, three or more TPR motifs form a TPR domain that recognizes short stretches of primary amino acid sequence at the COOH termini of their target proteins, −EEVD in Hsp70 and Hsp90 and −SKL in peroxisomal proteins.

    “In the case of two TPR-containing proteins, the Hsp70/Hsp90 organizing protein Hop and the peroxisomal import receptor PAS8, three or more TPR motifs form a TPR domain that recognizes short stretches of primary amino acid sequence at the COOH termini of their target proteins, −EEVD in Hsp70 and Hsp90 and −SKL in peroxisomal proteins, respectively (Terlecky et al. 1995; Scheufler et al. 2000).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Terlecky et al. 1995 source

      Not checked in the free run.

    • cites Scheufler et al. 2000 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Kinesin is required for axonal transport in neuronal cells.

    “Genetic studies in Caenorhabditis elegans, Drosophila melanogaster, and mice have failed to identify the primary cargo of conventional kinesin although, they have demonstrated that kinesin is required for axonal transport in neuronal cells (Saxton et al. 1991; Gho et al. 1992; Patel et al. 1993; Hurd and Saxton 1996; Hurd et al. 1996; Gindhart et al. 1998; Tanaka et al. 1998; Rahman et al. 1999).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Saxton et al. 1991 source

      Not checked in the free run.

    • cites Gho et al. 1992 source

      Not checked in the free run.

    • cites Patel et al. 1993 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    Scaffolding proteins assemble multiprotein complexes at great distances from their final functional locations.

    “scaffolding proteins assemble multiprotein complexes at great distances from their final functional locations.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Scaffolds and their associated proteins are required not only for localized signal transduction but also for regulating the motor that delivers them.

    “scaffolds and their associated proteins are required not only for localized signal transduction but also for regulating the motor that delivers them.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    Binding of JIPs to the TPR motifs in the tail of kinesin may unfold the native kinesin protein and activate it for MT binding.

    “the binding of JIPs to the TPR motifs in the tail of kinesin may unfold the native kinesin protein and activate it for MT binding.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The results do not exclude that there are regions in kinesin that interact with other cargoes.

    “they do not exclude that there are regions in kinesin that interact with other cargoes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    KLCs play a role both in directing cargo binding and in regulating motor activity.

    “the KLCs would play a role both in directing cargo binding and in regulating motor activity (Verhey et al. 1998).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Verhey et al. 1998 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Kinesin and JIPs may be involved in neuronal migration, pathfinding, and synaptogenesis.

    “rather, kinesin and JIPs may be involved in neuronal migration, pathfinding, and synaptogenesis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationreasoning

    Fusion of the transported vesicle with the plasma membrane would expose the receptor to its extracellular ligand, which may activate the JNK signaling cascade, which may in turn inactivate kinesin.

    “the fusion of the transported vesicle with the plasma membrane would expose the receptor, e.g., ApoER2, to its extracellular ligand, e.g., Reelin. This may result in the activation of the JNK signaling cascade, which may in turn inactivate kinesin”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    The bound cargo could stabilize the active state of the motor complex.

    “The bound cargo could then stabilize the active state of the motor complex”
    Quote in the paperNot a substantial claim
28 of 28

  • The authors state this as an assumption.

    Expression of the KLC TPR motifs acts as a dominant negative by binding kinesin cargo and preventing its transport because the construct lacks an attached motor domain.

    “One region of kinesin that could act as a dominant negative is that containing the TPR motifs of KLC; this region should bind to kinesin's cargo and prevent cargo transport to the correct location due to the lack of an attached motor domain.”

  • The authors state this as an assumption.

    The KHC-891 construct lacks only the autoinhibitory domain and still contains the regions necessary for motor function and cargo binding.

    “presumably because this construct is lacking only the autoinhibitory domain and still contains the regions necessary for motor function and cargo binding.”

  • The authors state this as an assumption.

    ApoER2 in the high speed supernatant fraction is associated with small vesicles that do not pellet under these conditions.

    “a small fraction of ApoER2 remains in the high speed supernatant fraction, presumably associated with small vesicles that do not pellet under these conditions (data not shown).”

  • The paper relies on this without support.

    The JIP scaffolding complex includes DLK and ApoER2.

    “the JIP scaffolding complex, which includes DLK and ApoER2, is preassembled before being transported by kinesin”
4 of 4

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?

  • Postsynaptic JIP and Tiam1 could be involved in mediating the effects of IDOL-ApoER2 axis on Rac1 activity.

    “Our data suggest that postsynaptic JIP (Stockinger et al., 2000; Verhey et al., 2001) and Tiam1 (Buchsbaum et al., 2002) could be involved in mediating the effects of IDOL-ApoER2 axis on Rac1 activity.”

    From The E3 ubiquitin ligase IDOL regulates synaptic ApoER2 levels and is important for plasticity and learning (2017) · cites this paper as Verhey et al., 2001

    The Results section ('Direct Interaction of KLC and the JIP Proteins'; page unavailable) says JIPs are enriched at synaptic junctions and that JIP-1 and JIP-2 interact with ApoER2. It does not establish that JIP is specifically postsynaptic. The proposed IDOL–ApoER2–Rac1 mechanism is framed as the citing authors’ suggestion, not as a finding of this source. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • 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).”

    From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Verhey et al., 2001

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Proposed model is cited as both Fig. 7 A and Fig. 8

    Minor

    The same motor-scaffold-vesicle model is attributed to Fig. 7 A here but to Fig. 8 earlier in the Discussion.

  • KIF17 discussion points to a figure described as a kinesin coprecipitation experiment

    Minor

    The KIF17-NMDA receptor statement cites Fig. 7 A, but the Results describe that figure as showing coprecipitation of kinesin with JIP-1 and DLK, not KIF17.

2 of 2

Cites

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Related

Authors
Verhey, K. J., Meyer, D., Deehan, R., Blenis, J., Schnapp, B. J., Rapoport, T. A., & Margolis, B.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Harvard University (US)
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2001-03-05
Volume
152
Issue
5
Pages
959-970
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.152.5.959
PMC
PMC2198804
OpenAlex
W2096910934
Semantic Scholar
337a2b34613d2d6553343f97e49358983c027894
Cited by
609
References
89
Citations by year
2026: 7 · 2025: 10 · 2024: 4 · 2023: 11 · 2022: 14 · 2021: 16 · 2020: 17 · 2019: 8 · 2018: 16 · 2017: 19 · 2016: 16 · 2015: 14 · 2014: 29 · 2013: 19 · 2012: 17
FWCI
18.58
Type
journal article
Language
en
Open access
Locations
  • The Journal of Cell Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
kinesin, kinesin light chain, JNK signaling, tetratricopeptide repeats, cargo binding, microtubule transport, presynaptic terminals, DLK, Reelin receptors, ApoER2
MeSH terms
Reelin Protein, Amino Acid Sequence, Animals, Binding Sites, Carrier Proteins, Cell Line, Models, Biological, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Neurons, Precipitin Tests, Protein Binding, Signal Transduction, Sequence Alignment, Kinesins, Receptors, Lipoprotein, Molecular Motor Proteins, Two-Hybrid System Techniques, Amino Acid Motifs, MAP Kinase Kinase Kinases, LDL-Receptor Related Proteins, Adaptor Proteins, Signal Transducing, Mice, Rats

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Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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