PTK7-Src signaling at epithelial cell contacts mediates spatial organization of actomyosin and planar cell polarity.
Actomyosin contractility plays a key role in tissue morphogenesis. During mammalian development, PTK7 regulates epithelial morphogenesis and planar cell polarity (PCP) through modulation of actomyosin contractility, but the underlying mechanism is unknown. Here, we show that PTK7 interacts with the tyrosine kinase Src and stimulates Src signaling along cell-cell contacts. We further identify ROCK2 as a target of junctional PTK7-Src signaling. PTK7 knockdown in cultured epithelial cells reduced the level of active Src at cell-cell contacts, resulting in delocalization of ROCK2 from cell-cell contacts and decreased junctional contractility, with a concomitant increase in actomyosin on the basal surface. Moreover, we present in vivo evidence that Src family kinase (SFK) activity is critical for PCP regulation in the auditory sensory epithelium and that PTK7-SFK signaling regulates tyrosine phosphorylation of junctional ROCK2. Together, these results delineate a PTK7-Src signaling module for spatial regulation of ROCK activity, actomyosin contractility, and epithelial PCP.
Department of Cell Biology, P.O. Box 800732, University of Virginia, Charlottesville, VA 22908, USA.
Anna
A
Andreeva
Department of Cell Biology, P.O. Box 800732, University of Virginia, Charlottesville, VA 22908, USA.
Jianyi
J
Lee
Department of Microbiology, Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA.
Madhura
M
Lohia
School of Life Sciences, Peking University, Beijing, China, 100871.
Xiaoji
X
Wu
Department of Microbiology, Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA.
Ian G
IG
Macara
Department of Cell Biology, P.O. Box 800732, University of Virginia, Charlottesville, VA 22908, USA. Electronic address: xl6f@virginia.edu.
Xiaowei
X
Lu
D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D007365:Intercellular Junctions / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism
D000205:Actomyosin; D020794:Receptor Protein-Tyrosine Kinases; D054460:rho-Associated Kinases