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Nedd4 regulates cell motility through modulation of vesicular trafficking and focal adhesion targeting of βPix
Author(s) -
Park Dongeun,
Lee Seung Joon,
Na Youn
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a234
Subject(s) - nedd4 , focal adhesion , microbiology and biotechnology , ubiquitin ligase , endosome , ubiquitin , signal transducing adaptor protein , cdc42 , motility , cell adhesion , adhesion , chemistry , biology , signal transduction , biochemistry , intracellular , organic chemistry , gene
βPix functions as a regulator of Rac/Cdc42 small GTPases, and also as an adaptor protein to form multimolecular complexes by interacting with other signaling molecules. These molecular complexes are recruited to sites where their activities are required. βPix is known to involve in the process of focal adhesion assembly and turnover through recruiting Pak kinase, Arf‐GAP proteins. However, little is known regarding the precise mechanism of regulating βPix translocation toward adhesion sites. Here we show that, a HECT type ubiquitin E3 ligase, Nedd4 interacts with βPix and this interaction induces polyubiquitination and subsequent degradation of βPix by proteasome complexes. Besides ubiquitin‐mediated degradation, Nedd4 is also important for regulating the trafficking and targeting of βPix. Tracing the subcellular localization revealed that βPix is targeted to focal adhesions and membranes via recyling endosomes. Overexpression of Nedd4 resulted in retention of βPix on Rab5‐positive endosomes, decreasing βPix targeting to focal adhesions. Conversely, knockdown of Nedd4 led to enhanced focal adhesion formation and impaired motility. These findings demonstrate that Nedd4 regulates focal adhesion turnover through modulating vesicular trafficking of βPix.