Figure 3.

Cell–cell adhesions regulate leader and follower cell polarity. Leader cells are shown in dark green, follower cells in lighter green. See text for details. (A1) Mature adherens junctions (AJs) suppress activity of RhoA, Rac1, and cdc42. Cell–extracellular matrix (ECM) adhesions at the leading edge recruit βPIX, resulting in the activation of cdc42, Rac1, and cross talk with PI3K. RhoA also acts at the leading edge. Polarized activity of RhoGTPases causes polarized pseudopodia extension, recruitment of polarity proteins, and reorientation of microtubules. (A2) AJ between leader cell and follower cells sequester and inhibit activation of integrins, leading to preferential activity at the leading edge. (B) Polarized RhoGTPase activity in follower cells. Follower cells extend frontal cryptic lamellipodia underneath anterior cells, where basal nascent AJs promote Rac1 activity, possibly via Tiam1, and inhibit RhoA via myosin IXa. Tight junctions at the rear bind Merlin, leaving Rich1 available to inhibit Rac1. At the front, tension on the tight junctions dissociates Merlin and recruits Rich1, leading to derepression of Rac1. (C) Cohesive polarization in peripheral follower cells causes the assembly of a supracellular contractile actomyosin cable. Rho-ROCK signaling is inhibited at internal cell–cell contacts by DDR1, E-cadherin, or Crumbs, leading to activation of myosin light chain and actomyosin at the cell periphery.