WISp39 binds phosphorylated Coronin 1B to regulate Arp2/3 localization and Cofilin-dependent motility

Abstract

WISp39 associates with Hsp90, Coronin 1B, and Slingshot phosphatase to regulate Cofilin activation and Arp2/3 complex localization at the leading edge of migrating cells.

PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front

“…This effect was similar to that of cells lacking Coronin 1B, an F-actin-binding protein that is localized to the leading edge of migrating fibroblasts (35). Cells that lacked PLEKHG3 had a longer shape, similar to that observed in cells lacking other well-known proteins, such as Cofilin (36) or WISp39 (37), that are localized to the leading edge. There was no significant difference in the actin structures of the H9 and PLEKHG3 −/− cells.…”

Competition and collaboration between different actin assembly pathways allows for homeostatic control of the actin cytoskeleton

“…F-actin disassembly and/ or severing via ADF/cofilin yields polymerization competent monomers 12,34 as well as yielding free polymerization-competent barbed ends. 35,36 The role of the cofilin phosphatase Slingshot 37,38 and the coronin 39 family of proteins may be major factors in sensing F-actin and in regulating the size of the G-actin pool. Furthermore, the activities of cofilin and the Arp2/3 complex are synergistic 34,40 and both are required for proper lamellipodia function, [41][42][43] so it seems that polymerization-competent actin generated by disassembly near membranes may be primed for the nucleation of new daughter filaments.…”

WISp39 and Hsp90: actin' together in cell migration

“…Our recent study has revealed two new important players in cellular motility. We have found that WISp39 (Waf1 Cip1 stabilizing protein 39), an Hsp90 binding protein we had discovered [ 4 ], coordinates Coronin 1B, Arp2/3 complex and Cofilin activity in the lamellipodia to achieve directed cell motility [ 5 ]. WISp39 is recruited to actin-enriched cell protrusions which contain the Arp2/3 complex and Coronin 1B.…”

“…WISp39 is recruited to actin-enriched cell protrusions which contain the Arp2/3 complex and Coronin 1B. Its knockdown results in the loss of directional motility and cell polarity, accompanied by profound changes in cell morphology [ 5 ]. Rescue of WISp39 function in WISp39 siRNA-treated cells restores directionality of motility to control levels.…”

“…Rescue of WISp39 function in WISp39 siRNA-treated cells restores directionality of motility to control levels. Most interestingly, we found that Hsp90 is an important component of the regulatory complex, as WISp39 mutants that do not bind Hsp90 cannot rescue the directionality defect [ 5 ]. Although Hsp90 has been shown to bind actin, and to increase the stability of proteins that control actin dynamics, its role in cell motility has not received much attention.…”