PMID- 25800056 OWN - NLM STAT- MEDLINE DCOM- 20150616 LR - 20201209 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 208 IP - 7 DP - 2015 Mar 30 TI - WISp39 binds phosphorylated Coronin 1B to regulate Arp2/3 localization and Cofilin-dependent motility. PG - 961-74 LID - 10.1083/jcb.201410095 [doi] AB - We previously identified Waf1 Cip1 stabilizing protein 39 (WISp39) as a binding partner for heat shock protein 90 (Hsp90). We now report that WISp39 has an essential function in the control of directed cell migration, which requires WISp39 interaction with Hsp90. WISp39 knockdown (KD) resulted in the loss of directional motility of mammalian cells and profound changes in cell morphology, including the loss of a single leading edge. WISp39 binds Coronin 1B, known to regulate the Arp2/3 complex and Cofilin at the leading edge. WISp39 preferentially interacts with phosphorylated Coronin 1B, allowing it to complex with Slingshot phosphatase (SSH) to dephosphorylate and activate Cofilin. WISp39 also regulates Arp2/3 complex localization at the leading edge. WISp39 KD-induced morphological changes could be rescued by overexpression of Coronin 1B together with a constitutively active Cofilin mutant. We conclude that WISp39 associates with Hsp90, Coronin 1B, and SSH to regulate Cofilin activation and Arp2/3 complex localization at the leading edge. CI - (c) 2015 Howell et al. FAU - Howell, Michael AU - Howell M AD - Sanford-Burnham Medical Research Institute, La Jolla, CA 92037. FAU - Brickner, Howard AU - Brickner H AD - Sanford-Burnham Medical Research Institute, La Jolla, CA 92037. FAU - Delorme-Walker, Violaine D AU - Delorme-Walker VD AD - The Scripps Research Institute, La Jolla, CA 92037. FAU - Choi, Justin AU - Choi J AD - Sanford-Burnham Medical Research Institute, La Jolla, CA 92037. FAU - Saffin, Jean-Michel AU - Saffin JM AD - Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037. FAU - Miller, Daniel AU - Miller D AD - Sanford-Burnham Medical Research Institute, La Jolla, CA 92037. FAU - Panopoulos, Andreas AU - Panopoulos A AD - Sanford-Burnham Medical Research Institute, La Jolla, CA 92037. FAU - DerMardirossian, Celine AU - DerMardirossian C AD - The Scripps Research Institute, La Jolla, CA 92037. FAU - Fotedar, Arun AU - Fotedar A AD - Sanford-Burnham Medical Research Institute, La Jolla, CA 92037. FAU - Margolis, Robert L AU - Margolis RL AD - Sanford-Burnham Medical Research Institute, La Jolla, CA 92037. FAU - Fotedar, Rati AU - Fotedar R AD - Sanford-Burnham Medical Research Institute, La Jolla, CA 92037 rfotedar@sanfordburnham.org. LA - eng GR - R01 CA108947/CA/NCI NIH HHS/United States GR - CA108947/CA/NCI NIH HHS/United States GR - CA101810/CA/NCI NIH HHS/United States GR - R01 GM088716/GM/NIGMS NIH HHS/United States GR - R01 CA101810/CA/NCI NIH HHS/United States GR - GM088716/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150323 PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Actin Depolymerizing Factors) RN - 0 (Actin-Related Protein 2-3 Complex) RN - 0 (FKBPL protein, human) RN - 0 (HSP90 Heat-Shock Proteins) RN - 0 (Microfilament Proteins) RN - 0 (RNA, Small Interfering) RN - 145420-64-0 (coronin proteins) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.1.3.16 (slingshot phosphatase 2, human) RN - EC 5.2.1.- (Tacrolimus Binding Proteins) RN - EC 5.2.1.8 (Immunophilins) SB - IM MH - Actin Depolymerizing Factors/genetics/*metabolism MH - Actin-Related Protein 2-3 Complex/*metabolism MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Enzyme Activation/genetics MH - HEK293 Cells MH - HSP90 Heat-Shock Proteins/metabolism MH - HeLa Cells MH - Humans MH - Immunophilins/genetics/*metabolism MH - Microfilament Proteins/biosynthesis/*metabolism MH - Phosphoprotein Phosphatases MH - Phosphorylation MH - Protein Binding MH - RNA Interference MH - RNA, Small Interfering MH - Tacrolimus Binding Proteins PMC - PMC4384738 EDAT- 2015/03/25 06:00 MHDA- 2015/06/17 06:00 PMCR- 2015/09/30 CRDT- 2015/03/25 06:00 PHST- 2015/03/25 06:00 [entrez] PHST- 2015/03/25 06:00 [pubmed] PHST- 2015/06/17 06:00 [medline] PHST- 2015/09/30 00:00 [pmc-release] AID - jcb.201410095 [pii] AID - 201410095 [pii] AID - 10.1083/jcb.201410095 [doi] PST - ppublish SO - J Cell Biol. 2015 Mar 30;208(7):961-74. doi: 10.1083/jcb.201410095. Epub 2015 Mar 23.