PTK7-Src Signaling at Epithelial Cell Contacts Mediates Spatial Organization of Actomyosin and Planar Cell Polarity

• PTK7 stimulates Src kinase signaling at epithelial cell-cell contacts
• PTK7-Src signaling regulates junctional contractility in part through ROCK2
• Junctional Src signaling is critical for PCP in the mouse inner ear
• PTK7-Src signaling regulates phosphorylation of junctional ROCK2 at Y722 in vivo

SummaryActomyosin 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.

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