Fig 5.

Proposed model for the Cin1-mediated endocytic pathway, which regulates actin organization through the collective functions of Cin1, Cdc42, Rac1, and Wsp1. Cin1 is a multimodular adaptor protein proposed to regulate endocytosis, exocytosis, and signaling through interactions with several other proteins (47). Cin1 activates Cdc42 through the DH (Rho-GEF) domain; Cdc42, in turn, activates Wsp1 to promote Arp2/3-mediated actin polymerization. In addition to Cdc42, Wsp1 can also be an effector of Rac1 to regulate endocytosis and vacuole morphology. A possible effect of Cin1-DH on Rac1 has not been substantiated. Cin1 also activates Wsp1 through direct binding between the SRC homology 3 (SH3) (Cin1) and proline-rich (PR) (Wsp1) domains. Moreover, Cin1 may promote the extension of the branched actin filaments by binding directly to Arp2/3 homologs through the A domain and to monomeric actin (G-actin) through the WASP homology 2 (WH2) domain.