Document Detail


PTK7 regulates myosin II activity to orient planar polarity in the mammalian auditory epithelium.
MedLine Citation:
PMID:  22560610     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Planar cell polarity (PCP) signaling is a key regulator of epithelial morphogenesis, including neural tube closure and the orientation of inner ear sensory hair cells, and is mediated by a conserved noncanonical Wnt pathway. Ptk7 is a novel vertebrate-specific regulator of PCP, yet the mechanisms by which Ptk7 regulates mammalian epithelial PCP remain poorly understood.
RESULTS: Here we show that, in the mammalian auditory epithelium, Ptk7 is not required for membrane recruitment of Dishevelled 2; Ptk7 and Frizzled3/Frizzled6 receptors act in parallel and have opposing effects on hair cell PCP. Mosaic analysis identified a requirement of Ptk7 in neighboring supporting cells for hair cell PCP. Ptk7 and the noncanonical Wnt pathway differentially regulate a contractile myosin II network near the apical surface of supporting cells. We provide evidence that this apical myosin II network exerts polarized contractile tension on hair cells to align their PCP, as revealed by asymmetric junctional recruitment of vinculin, a tension-sensitive actin binding protein. In Ptk7 mutants, compromised myosin II activity resulted in loss of planar asymmetry and reduced junctional localization of vinculin. By contrast, vinculin planar asymmetry and stereociliary bundle orientation were restored in Fz3(-/-);Ptk7(-/-) double mutants.
CONCLUSIONS: These findings suggest that PTK7 acts in conjunction with the noncanonical Wnt pathway to orient epithelial PCP through modulation of myosin II-based contractile tension between supporting cells and hair cells.
Authors:
Jianyi Lee; Anna Andreeva; Conor W Sipe; Lixia Liu; Amy Cheng; Xiaowei Lu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-03
Journal Detail:
Title:  Current biology : CB     Volume:  22     ISSN:  1879-0445     ISO Abbreviation:  Curr. Biol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-08     Completed Date:  2012-10-15     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  9107782     Medline TA:  Curr Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  956-66     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Cell Biology, P.O. Box 800732, University of Virginia, Charlottesville, VA 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / metabolism
Animals
Cell Polarity*
Frizzled Receptors / genetics,  metabolism
HEK293 Cells
Hair Cells, Auditory, Inner / cytology,  metabolism*
Humans
MAP Kinase Signaling System
Mice
Mutation
Myosin Type II / metabolism*
Phosphoproteins / metabolism
Receptor Protein-Tyrosine Kinases / genetics,  metabolism*
Vinculin / metabolism
Wnt Proteins / metabolism*
Grant Support
ID/Acronym/Agency:
R01 DC009238/DC/NIDCD NIH HHS; R01 DC009238/DC/NIDCD NIH HHS; T32 GM008136/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Frizzled Receptors; 0/Fzd3 protein, mouse; 0/Phosphoproteins; 0/Wnt Proteins; 0/dishevelled proteins; 125361-02-6/Vinculin; EC 2.7.10.1/Ptk7 protein, mouse; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 3.6.1.-/Myosin Type II
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