Regulation of Rho GTPases from the lateral sides of migrating cells.

Migratory polarity and epithelial polarity share many common regulatory mechanisms. Rho GTPases play a key role in modulating cell polarity, which in migrating cells has been conventionally studied along the solitary front-rear axis. In recent work, we discovered that Prickle1 (Pk1), a core com-ponent of planar cell polarity (PCP) signaling, mediates a novel lateral signaling pathway that coordinates multi-axial protrusive activities from the lateral cortex of migrating cancer cells. We identified that Arhgap21 and 23 are essential effectors of Pk1, and that lateral signaling regulates RhoA, actomyosin and focal adhesion dynamics. Interestingly, we showed that lateral signaling coordinates shape dynamics that are critical during cell migration and function orthogonally to front-rear directional polarity.