Fig. 6.

Postulated Dual Signaling Pathway for Sema3F-induced Spine Pruning through Rac1 and RhoA.

Sema3F induced signaling begins with binding between the NrCAM-Npn2-PlexA3 holoreceptor and ligand Sema3F. Sema3F induces clustering and conformational changes that initiates the RapGAP activity of the intracellular portion of PlexA3, leading to the inactivation of Rap1. It is speculated that a Rap-dependent RhoGAP is inactivated allowing RhoA-GTP to be active. GTP-bound RhoA binds ROCK1/2 which then activates Myosin II by phosphorylating the myosin light chain (MLC). Phosphorylated MLC II induces actomyosin contraction which may create tension that leads to actin depolymerization. To provide the framework necessary for contractile force, Tiam1 is recruited to exchange GDP for GTP on Rac1. Rac1 then activates PAK1-3. PAK can then phosphorylate LIMK1/2, which phosphorylates Cofilin1, inactivating it. Cofilin inactivation leads to elongation of actin filaments providing the framework for tension generation.