WISp39 binds phosphorylated Coronin 1B to regulate Arp2/3 localization and Cofilin-dependent motility
Copyright policy )WISp39 binds phosphorylated Coronin 1B to regulate Arp2/3 localization and Cofilin-dependent motility
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.
- University of California, San Francisco United States
- University of California System United States
- SANFORD-BURNHAM MEDICAL RESEARCH INSTIT
- University of California, San Diego United States
- University of California, San Diego United States
Microfilament Proteins, Actin-Related Protein 2-3 Complex, Enzyme Activation, Tacrolimus Binding Proteins, HEK293 Cells, Actin Depolymerizing Factors, Cell Movement, Cell Line, Tumor, Phosphoprotein Phosphatases, Humans, RNA Interference, HSP90 Heat-Shock Proteins, Immunophilins, Phosphorylation, RNA, Small Interfering, Research Articles, HeLa Cells, Protein Binding
Microfilament Proteins, Actin-Related Protein 2-3 Complex, Enzyme Activation, Tacrolimus Binding Proteins, HEK293 Cells, Actin Depolymerizing Factors, Cell Movement, Cell Line, Tumor, Phosphoprotein Phosphatases, Humans, RNA Interference, HSP90 Heat-Shock Proteins, Immunophilins, Phosphorylation, RNA, Small Interfering, Research Articles, HeLa Cells, Protein Binding
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