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Neuronal specific βPix‐b stimulates actin‐dependent processes via the interaction between its PRD and WH1 domain of N‐WASP
Author(s) -
Park Joohyun,
Kim Yoonju,
Park Zee Yong,
Park Dongeun,
Chang Sunghoe
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22863
Subject(s) - guanine nucleotide exchange factor , wiskott–aldrich syndrome protein , actin , microbiology and biotechnology , gene isoform , biology , rac1 , chemistry , actin cytoskeleton , biochemistry , gtpase , cytoskeleton , cell , gene , signal transduction
βPix, a Pak‐interacting nucleotide exchange factor (Cool‐1/p85SPR), is a Cdc42/Rac1‐specific guanine nucleotide exchange factor (GEF) involved in various actin‐related processes. Many previous studies have focused on ubiquitously expressed βPix‐a, while the role of the neuronal‐specific isoform βPix‐b is still unknown, especially whether its role is distinct from or similar to βPix‐a. Here we show that unlike βPix‐a, overexpression of βPix‐b stimulates actin‐dependent comet formation in BHK21 cells. This effect is attributed to the interaction between its proline‐rich domain (PRD) and the WH1 domain of N‐WASP. In addition, we show that overexpression of βPix‐b stimulates actin‐dependent dendritic spine formation in rat hippocampal neurons in culture, a formation that is blocked by co‐expression of the WH1 domain of N‐WASP or the PRD of βPix‐b. Knocking‐down endogenous expression of βPix‐b by shRNA reduced the number of dendritic spines, which were rescued only by PRD‐containing βPix‐b mutants. GEF activity of βPix‐b is also required for these effects. The results show that neuronal‐specific βPix‐b stimulates actin‐dependent processes in cells via the interaction between its PRD and the WH1 domain of N‐WASP. Our results identify N‐WASP as the first protein shown to interact with the PRD of βPix‐b, raising the possibility that, as an N‐WASP WH1‐binding protein, βPix‐b may regulate N‐WASP's activity in cells. J. Cell. Physiol. 227: 1476–1484, 2012. © 2011 Wiley Periodicals, Inc.