Figure 4. Semas Employ Plexins to Direct Repulsion.

(a) Plexins. Domain names are from SMART (http://smart.embl-heidelberg.de) except GAP, GTPase activating protein; C1, conserved 1; C2, conserved 2; RBD, Rho GTPase binding domain; MICAL-IR, MICAL interacting region. (b) Sema/Plex-mediated effects on cell adhesion. The current model is that 1) the Plexin GAP is activated by binding of both Sema and a Rac GTPase to the Plexin extracellular and intracellular regions, respectively, 2) the Plexin GAP activity locally enriches for the GDP-bound form of Ras family GTPases, which 3) inactivates (through “inside-out” signaling) integrin-extracellular matrix-mediated adhesion. (c) Sema effects on microtubules. The current model is that Semas “turn-on” tau-mediated microtubule alterations and “turn-off” CRMP-mediated tubulin assembly. (d) Current models suggest that Sema-mediated F-actin alterations occur by limiting actin polymerization (left) and/or by inducing actin depolymerization by regulating the levels of active cofilin (right). A few other actin-associated proteins including myosin II and ERM are involved in Sema-mediated repulsion (Gallo 2008; Mintz et al. 2008; Schlatter et al. 2008), but their effects appear secondary to directly inducing F-actin disassembly (Brown et al. 2009; Gallo 2006; Takamatsu et al. 2010).