CoChat
Sign Up
Cited by 25Axon Guidance and Neuronal SignalingNeurogenesis and neuroplasticity mechanismsProtein Kinase Regulation and GTPase Signaling

Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation

Open access
Yang, Rui, Kong, Eryan, Jin, Jing, Hergovich, Alexander, Püschel, Andreas W.·2014·Journal of Cell Science
DOI 10.1242/jcs.146696PMC PMC4132390
Open this paper in CoChat — free account

Abstract

The morphology and polarized growth of cells depend on pathways that control the asymmetric distribution of regulatory factors. The evolutionarily conserved Ndr kinases play important roles in cell polarity and morphogenesis in yeast and invertebrates but it is unclear if they perform a similar function in mammalian cells. Here we analyze the function of mammalian Ndr1 and 2 in the establishment of polarity in neurons. We show that they act downstream of the tumor suppressor Rassf5 and upstream of the polarity protein Par3. Rassf5 and Ndr1/2 are required during the polarization of hippocampal neurons to prevent the formation of supernumerary axons. Mechanistically, the Ndr kinases act by phosphorylating Par3 at Ser383 to inhibit the interaction with dynein. Thereby they polarize the distribution of Par3 and reinforce axon specification. Our results identify a novel Rassf5/Ndr/Par3 signaling cascade that regulates the transport of Par3 during the establishment of neuronal. Their role in neuronal polarity suggests that Ndr kinases perform a conserved function as regulators of cell polarity.

AI snapshot

Written from the paper’s full text.

TL;DR

This paper identifies a Rassf5–Ndr–Par3 signaling cascade that regulates neuronal polarity by phosphorylating Par3 at Ser383 and altering its dynein-dependent transport. Loss of Rassf5 or Ndr1/2 causes supernumerary axons, while phospho-mimetic Par3 rescues the polarity defect.

Key findings

  • Simultaneous knockdown of Ndr1 and Ndr2 in hippocampal neurons reduced neurons with a single axon from 74±2% to 50±2% and increased supernumerary axons from 23±2% to 47±1%; RNAi-resistant Ndr1 or Ndr2 rescued the phenotype.
  • Rassf5 knockdown increased multiple-axon neurons from 24±2% to 50±4%, rescued to 23±4% by RNAi-resistant Rassf5; Rassf5−/− cultures showed 41±2% multiple axons versus 13±3% in Rassf5+/− cultures.
  • Ndr2 phosphorylated Par3 at Ser383; phospho-Ser383-Par3 signal in axons was reduced from 80±14 a.u. in controls to 7±2 a.u. after Ndr1/2 knockdown and from 36±4 a.u. to 9±2 a.u. after Rassf5 knockdown.
  • Par3-S383,1196D rescued Ndr1/2 knockdown (multiple axons 50±3% to 28±1%) and Rassf5 knockdown (43±1% to 19±2%), whereas Par3-S383,1196A did not; Par3-S383D localized preferentially to axons (49±1% of signal) versus Par3-S383A (29±4%), and S383D abolished Dlic2 binding.

Methods

  • Primary E18 hippocampal neuron cultures were transfected with shRNAs against Ndr1, Ndr2, or Rassf5 and analyzed at 3 DIV for axon number using Tau-1 and MAP2 staining; rescue experiments used RNAi-resistant and phospho-mutant constructs.
  • Rassf5−/− mice and ex vivo electroporation of E14.5 cortical slices with live imaging were used to assess neuronal polarization and migration.
  • Biochemistry included GST pulldowns, immunoprecipitation, in vitro kinase assays, mass spectrometry, and a phospho-Ser383-Par3 antibody.

Limitations

  • The paper does not include a dedicated limitations section. It states that constitutive Rassf5 knockout may allow compensatory changes, that future work is needed to dissect Rassf5/Mst signaling in detail, and that an antibody against phospho-Ser1196-Par3 could not be obtained.
  • Evident from the text: much of the mechanistic evidence relies on cultured hippocampal neurons, shRNA knockdown, and overexpression/rescue constructs, with cortical slice electroporation rather than direct in vivo demonstration of supernumerary axons in the Rassf5 knockout brain.

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

Integrity signals

Registry

Crossref · 10.1242/jcs.146696

Cites

66 of 66 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

14 of 39 cited sources checked · 7 supported · 1 flagged · accuracy not yet measured

  • Premisecitation
    § DISCUSSION

    Par3 acts as a microtubule-binding protein that bundles and stabilizes microtubules to promote axon extension.

    “Recently, it was shown that Par3 also acts as a microtubule-binding protein that bundles and stabilizes microtubules to promote axon extension (Chen et al., 2013).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Chen et al., 2013 source

      The Results section reports that mPar3 directly binds and bundles microtubules, and the Discussion says it stabilizes them in the emerging axon. The paper links this activity to axon specification and neuronal polarization, but does not establish that it promotes axon extension; the Results instead report impaired axonal outgrowth with mPar3 overexpression. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation
    § DISCUSSION

    Par3's concentration-dependent oligomerization determines its ability to bind microtubules.

    “Its concentration-dependent oligomerization determines its ability to bind microtubules.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Chen et al., 2013 source
  • Premisecitation
    § DISCUSSION

    During the establishment of polarity, kinesin-2 transports Par3 into the axon where it is released after phosphorylation by Erk2.

    “During the establishment of polarity, kinesin-2 transports Par3 into the axon where it is released after phosphorylation by Erk2 (Funahashi et al., 2013).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Funahashi et al., 2013 source

      The passage on Par3 transport says kinesin-2 (KIF3A) carries Par3 toward the tip of a developing axon. The Methods and Results passage reports that ERK2 phosphorylates Par3 in the distal axon and weakens its binding to KIF3A. The Conclusion discusses unloading as a proposed mechanism, but does not establish that Par3 is released there after phosphorylation. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Findingown data
    § RESULTS

    After polarization, Ndr kinases are detectable mainly in the axon, with only weak signals in minor neurites.

    “After polarization, Ndr kinases were detectable mainly in the axon, and only weak signals were present in minor neurites (Fig. 1A).”
    Quote in the paperNot a substantial claim
  • Findingown data
    § DISCUSSION

    Ser383 phosphorylation of Par3 depends on Ndr1/2 and Rassf5.

    “Ser383 phosphorylation of Par3 depends on Ndr1/2 and Rassf5, and only the Ser383 Par3 phospho-mimic is sufficient to rescue the loss of Ndr kinases or the loss of Rassf5, whereas the non-phosphorylatable mutant did not show rescuing activity.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 16
  • May combine two claims. 22

  • Classified as probably not a substantial claim.

    Premisecitation
    § DISCUSSION

    The dynein-dependent transport of the Drosophila Par3 homolog Bazooka is required for the segregation of apically localized proteins during the establishment of epithelial polarity.

    “The dynein-dependent transport of the Drosophila Par3 homolog Bazooka is required for the segregation of apically localized proteins during the establishment of epithelial polarity (Harris and Peifer, 2005).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Harris and Peifer, 2005 source

      The Results section ‘Baz positioning also requires dynein-mediated basal-to-apical transport’ supports dynein’s role in positioning Baz during cellularization. But ‘aPKC and PAR-6 positioning is dynein independent’ reports that apical and basal proteins still segregate in dynein mutants during gastrulation, contrary to the claim that dynein-dependent Baz transport is required for their segregation. (LLM, conf=0.87)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

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

    Premisecitation
    § INTRODUCTION

    Mammalian Ndr1 and Ndr2 share a conserved kinase domain with Drosophila Warts and mammalian Lats1 and Lats2.

    “Mammalian Ndr1 (also known as STK38) and Ndr2 (also known as STK38L) share a conserved kinase domain with Drosophila Warts and mammalian Large tumor suppressor (Lats) 1 and 2 (Hergovich et al., 2006a; Hergovich et al., 2006b; Yu and Guan, 2013).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Hergovich et al., 2006a

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

    • cites Hergovich et al., 2006b

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

    • cites Yu and Guan, 2013 source

      The paper identifies mammalian Lats1/2 as orthologs of Drosophila Warts in its Hippo-pathway discussion and Table 1 (page unavailable). It does not state that Ndr1 or Ndr2 shares a conserved kinase domain with them; searches for Ndr1 and NDR kinase domain found no supporting passage. (LLM, conf=0.81)

      Experimental — accuracy not yet measured

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

    Premisecitation
    § INTRODUCTION

    Ndr kinases are conserved from yeast to human and act as components of an essential pathway.

    “The nuclear Dbf2-related (Ndr) kinases act as components of one of these essential pathways and are conserved from yeast to human (Hergovich et al., 2006b; Yu and Guan, 2013).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Hergovich et al., 2006b

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

    • cites Yu and Guan, 2013 source

      The passage describing the core Hippo pathway (indexed under Abstract; page unavailable) identifies Lats1/2 as components of a kinase cascade conserved between Drosophila and mammals. It does not identify them as Ndr kinases or establish conservation from yeast to humans, and it does not call the pathway essential. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

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

    Premisecitation
    § INTRODUCTION

    Mammalian Ndr kinases have been implicated in the regulation of centrosome duplication and in dendrite arborization and spine formation during neuronal development.

    “Mammalian Ndr kinases have been implicated in the regulation of centrosome duplication and in dendrite arborization and spine formation during neuronal development (Hergovich et al., 2007; Ultanir et al., 2012).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Hergovich et al., 2007 source
    • cites Ultanir et al., 2012 source

  • Classified as probably not a substantial claim.

    Premisecitation
    § INTRODUCTION

    A crucial step in neuronal differentiation is the transition from an unpolarized neuron with multiple short neurites to a polarized neuron with a single axon.

    “A crucial step in neuronal differentiation is the transition from an unpolarized neuron with multiple short neurites to a polarized neuron with a single axon (Barnes and Polleux, 2009).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Barnes and Polleux, 2009 source

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

    Premisecitation
    § DISCUSSION

    Ndr kinases and Par3 have been implicated in the regulation of centrosome duplication and orientation, respectively.

    “Ndr kinases and Par3 have been implicated in the regulation of centrosome duplication and orientation, respectively (Hergovich et al., 2007; Schmoranzer et al., 2009).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Hergovich et al., 2007 source
    • cites Schmoranzer et al., 2009 source

  • May combine two claims.

    Premisecitation
    § DISCUSSION

    Par3 interacts not only with KIF3A but also with the dynein subunit Dlic2.

    “Par3 interacts not only with KIF3A but also with the dynein subunit Dlic2 (Schmoranzer et al., 2009).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Schmoranzer et al., 2009 source

      The Results section, “Par3 associates with dynein” (page unavailable), reports that dynein light intermediate chain 2 (LIC2) co-immunoprecipitated with Par3, supporting the Dlic2 portion of the claim. Our copy does not establish the claimed interaction between Par3 and KIF3A; searches for KIF3A found no relevant passage. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

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

    Premisecitation
    § INTRODUCTION

    Hippocampal neurons go through five stages of differentiation.

    “Hippocampal neurons go through five stages of differentiation (Banker and Cowan, 1977; Dotti et al., 1988).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Banker and Cowan, 1977 source
    • cites Dotti et al., 1988 source

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

    Premisecitation
    § INTRODUCTION

    Disruption of Par3 localization by interfering with the kinesin-2-dependent transport of Par3 causes polarity defects in hippocampal neurons, showing that the restricted localization of Par3 to the axon is essential for neuronal polarity.

    “Disruption of Par3 localization by interfering with the kinesin-2-dependent transport of Par3 causes polarity defects in hippocampal neurons, showing that the restricted localization of Par3 to the axon is essential for neuronal polarity (Funahashi et al., 2013; Nishimura et al., 2004).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Funahashi et al., 2013 source
    • cites Nishimura et al., 2004 source

  • May combine two claims.

    Interpretationcitation
    § DISCUSSION

    The Ndr phosphorylation sites in Par3 (Ser383 and Ser1196) are novel and distinct from the sites for Aurora A, ROCK and Erk2 that regulate Par3 function in neuronal polarity.

    “The Ndr phosphorylation sites in Par3 are novel and distinct from the sites for Aurora A, ROCK and Erk2 that regulate its function in neuronal polarity (Chen et al., 2006; Funahashi et al., 2013; Khazaei and Püschel, 2009; Nakayama et al., 2008).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Chen et al., 2006 source
    • cites Funahashi et al., 2013 source
    • cites Khazaei and Püschel, 2009 source

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

    Premisecitation
    § INTRODUCTION

    One key pathway depends on the sequential activity of phosphatidylinositol 3-kinase and the GTPases Rap1 and Cdc42 that act through the Par polarity complex.

    “One key pathway depends on the sequential activity of phosphatidylinositol 3-kinase and the GTPases Rap1 and Cdc42 that act through the Par polarity complex (Garvalov et al., 2007; Schwamborn and Püschel, 2004).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Garvalov et al., 2007 source

      The Introduction (p. 1) places Cdc42 downstream of Rap1B in neuronal polarity, supporting that part of the proposed sequence. But the paper does not establish phosphatidylinositol 3-kinase as an upstream step, and its analysis of the Par3/Par6/aPKC complex found no consistent differences between Cdc42-knockout and wild-type neurons (p. 11). It therefore does not support the full pathway attributed to it. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites Schwamborn and Püschel, 2004 source

  • May combine two claims.

    Findingown data
    § DISCUSSION

    Only the Ser383 Par3 phospho-mimic is sufficient to rescue the loss of Ndr kinases or the loss of Rassf5, whereas the non-phosphorylatable mutant did not show rescuing activity.

    “Ser383 phosphorylation of Par3 depends on Ndr1/2 and Rassf5, and only the Ser383 Par3 phospho-mimic is sufficient to rescue the loss of Ndr kinases or the loss of Rassf5, whereas the non-phosphorylatable mutant did not show rescuing activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § DISCUSSION

    Par3-S383D is located preferentially in the axon, whereas the majority of Par3-S383A remains in the soma.

    “Par3-S383D is located preferentially in the axon, whereas the majority of Par3-S383A remains in the soma.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § RESULTS

    Simultaneous knockdown of both Ndr1 and Ndr2 disrupts neuronal polarity and results in the formation of multiple Tau-1-positive axons.

    “However, simultaneous knockdown of both Ndr1 and Ndr2 disrupted neuronal polarity and resulted in the formation of multiple Tau-1-positive axons.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § DISCUSSION

    Ndr kinases phosphorylate Par3 at Ser383 and Ser1196.

    “We identified two phosphorylation sites in Par3 for Ndr kinases (Ser383 and Ser1196) using kinase assays and mass spectrometry.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § DISCUSSION

    Par3 phosphorylated at Ser383 is highly concentrated in the distal axon and largely absent from dendrites.

    “Par3 phosphorylated at Ser383 is highly concentrated in the distal axon and largely absent from dendrites, which is consistent with the function of Par3 in axon specification.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § INTRODUCTION

    Ndr1 and Ndr2 show similar substrate specificity and appear to act redundantly.

    “Ndr1 and Ndr2 show similar substrate specificity and appear to act redundantly as suggested by the phenotype of knockout mice (Cornils et al., 2010; Hergovich et al., 2006a).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Cornils et al., 2010 source
    • cites Hergovich et al., 2006a

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

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

    Premisecitation
    § INTRODUCTION

    Ndr kinases play important roles in cell polarity and morphogenesis in yeast.

    “Ndr kinases play important roles in cell polarity and morphogenesis in yeast (Hergovich et al., 2006b), but their function in mammalian cells is less well studied.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hergovich et al., 2006b

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

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

    Premisecitation
    § INTRODUCTION

    Drosophila and C. elegans Ndr homologs Tricornered and SAX-1 are involved in patterning dendrites.

    “The Drosophila and Caenorhabditis elegans Ndr homologs Tricornered and SAX-1 are involved in patterning dendrites (Emoto et al., 2004; Emoto et al., 2006; Gallegos and Bargmann, 2004; He et al., 2005).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Emoto et al., 2004 source
    • cites Emoto et al., 2006 source
    • cites Gallegos and Bargmann, 2004 source

  • May combine two claims.

    Premisecitation
    § DISCUSSION

    A uniform distribution after overexpression of Par3 or a block of its KIF3A-dependent anterograde transport into the axon disrupts the establishment of neuronal polarity.

    “A uniform distribution after overexpression of Par3 or a block of its KIF3A-dependent anterograde transport into the axon disrupts the establishment of neuronal polarity (Nishimura et al., 2004; Shi et al., 2003).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Nishimura et al., 2004 source
    • cites Shi et al., 2003 source

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

    Interpretationcitation
    § DISCUSSION

    Dynein might perform a similar function in neurons to mediate the retrograde transport of Par3 and segregate dendritic and axonal properties.

    “Thus, dynein might perform a similar function in neurons to mediate the retrograde transport of Par3 and segregate dendritic and axonal properties.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given
    § INTRODUCTION

    Rassf5 acts upstream of the Ndr kinases and stimulates their activity.

    “Rassf5 acts upstream of the Ndr kinases and stimulates their activity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data
    § DISCUSSION

    Phosphorylation at Ser383 by Ndr kinases prevents the interaction of Par3 with dynein and thereby blocks its retrograde transport to the soma, which allows the accumulation of Par3 in a single neurite to promote axon formation.

    “Phosphorylation at Ser383 by Ndr kinases then prevents the interaction of Par3 with dynein and thereby blocks its retrograde transport to the soma, which allows the accumulation of Par3 in a single neurite to promote axon formation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § DISCUSSION

    As a consequence, Par3 continues to be equally distributed to all neurites, which results in the formation of supernumerary axons.

    “As a consequence, Par3 continues to be equally distributed to all neurites, which results in the formation of supernumerary axons.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning
    § DISCUSSION

    In the absence of Ndr kinases, Par3 Ser383 remains unphosphorylated and the retrograde transport of Par3 persists.

    “In the absence of Ndr kinases, Par3 Ser383 remains unphosphorylated and the retrograde transport of Par3 persists.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § ABSTRACT

    Ndr1 and Ndr2 act downstream of Rassf5 and upstream of Par3.

    “We show that they act downstream of the tumor suppressor Rassf5 and upstream of the polarity protein Par3 (also known as PARD3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § DISCUSSION

    Ser383 phosphorylation affects the localization and/or transport of Par3.

    “This difference in the distribution pattern suggests that Ser383 phosphorylation affects the localization and/or transport of Par3.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § INTRODUCTION

    The function of Par3 depends on its specific subcellular localization; it is present in all neurites at stage 2 but becomes restricted to the axon at stage 3.

    “The function of Par3 depends on its specific subcellular localization; it is present in all neurites at stage 2 but becomes restricted to the axon at stage 3 (Schwamborn and Püschel, 2004; Shi et al., 2003).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Schwamborn and Püschel, 2004 source
    • cites Shi et al., 2003 source

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

    Premisecitation
    § INTRODUCTION

    Several signaling cascades that direct the establishment of neuronal polarity have been identified.

    “Several signaling cascades that direct the establishment of neuronal polarity have been identified (Arimura and Kaibuchi, 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Arimura and Kaibuchi, 2007 source

  • May combine two claims.

    Premisecitation
    § DISCUSSION

    In stage 2 neurons, Par3 is present in all neurites but becomes restricted to the axon upon its formation at stage 3.

    “In stage 2 neurons, Par3 is present in all neurites but becomes restricted to the axon upon its formation at stage 3.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Nishimura et al., 2004 source
    • cites Shi et al., 2003 source

  • May combine two claims.

    Interpretationreasoning
    § DISCUSSION

    Par3 Ser383 is not phosphorylated in the remaining minor neurites, allowing its depletion from these processes by continued retrograde transport.

    “By contrast, Par3 Ser383 is not phosphorylated in the remaining minor neurites, allowing its depletion from these processes by continued retrograde transport.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning
    § DISCUSSION

    Rassf5 and Ndr kinases might also play important roles in other types of polarized cells, such as epithelial cells.

    “Taken together, we identify a novel function of Rassf5 and Ndr kinases, which might also play important roles in other types of polarized cells, such as epithelial cells, where Par3 performs an important function.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Par3 performs an important function in epithelial cells.
32 of 32

  • The paper relies on this without support.

    Par3 performs an important function in epithelial cells.

    “where Par3 performs an important function.”
1 of 1

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.

  • Cell line differs between the Dlic2 immunoprecipitation result and methods

    Minor

    The Dlic2 interaction experiment is described as using HEK 239T cells, whereas the immunoprecipitation methods specify HEK 293T cells. The text does not clarify which cell line was used.

1 of 1

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Yang, R., Kong, E., Jin, J., Hergovich, A., & Püschel, A. W.
Affiliations
  • University of Münster (DE)
  • University College London (GB)
Corresponding author
Püschel, Andreas W.
ORCID
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2014-01-01
Volume
127
Issue
Pt 16
Pages
3463-76
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.146696
PMC
PMC4132390
OpenAlex
W2071198165
Semantic Scholar
39fae687561a4c805e7e271e39ade3625ad8b75a
Cited by
25
References
66
Citations by year
2026: 1 · 2025: 5 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 6 · 2017: 1 · 2016: 3 · 2015: 2
FWCI
0.81
Type
journal article
Language
en
Open access
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion)
  • PubMed Central (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Wellcome Trust (090090/Z/09/Z)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
RASSF5, NDR kinase, NDR1, NDR2, STK38, Par3, PARD3, neuronal polarity, axon specification, hippocampal neurons, dynein, protein phosphorylation
MeSH terms
Animals, Neurons, Phosphorylation, Protein Binding, Signal Transduction, Cell Adhesion Molecules, Cell Polarity, Protein Serine-Threonine Kinases, Mice, Knockout, Cell Cycle Proteins, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Mice

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 2026-10-18.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-18.

Cited sources are checked by gpt-6-sol.

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 ›

Are you an author, or do you see a problem with this page? Request a review