WISp39 binds phosphorylated Coronin 1B to regulate Arp2/3 localization and Cofilin-dependent motility.
Bottom Line: 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 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.
Affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.Show MeSH
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Mentions: Because WISp39 promotes the dephosphorylation of Coronin 1B and Cofilin, the profound changes in cell morphology and directional migration observed in WISp39 KD cells may ultimately be a result of the loss of proper Coronin 1B and Cofilin activation and function, which in turn would affect Arp2/3 complex function. To test this, we attempted to rescue the phenotype of WISp39 KD by expressing constitutively active Cofilin(S3A) alone or in combination with Coronin 1B WT (Fig. 7). Cofilin(S3A) alone was unable to rescue the phenotype created by depletion of WISp39, as measured by morphology changes from apolar to bi- and multipolar cells (Fig. 7, C and E). In contrast, Cofilin(S3A) expressed together with Coronin 1B WT was able to rescue the elongated, irregular shape and multipolarity typical of WISp39 KD cells to the extent that they appeared similar to control cells (Fig. 7, D and E). Collectively, these results suggest that WISp39 plays an important role in regulating actin-dependent lamellipodial dynamics at the leading edge, by binding phosphorylated Coronin 1B in a complex with SSH and coordinating the activation of Cofilin and the regulation of the Arp2/3 complex.
Affiliation: Sanford-Burnham Medical Research Institute, La Jolla, CA 92037.