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Beta‐arrestin‐dependent localization of actin‐turnover proteins downstream of Protease‐Activated Receptor‐2
Author(s) -
Zoudilova Maria,
Ge Lan,
DeFea Kathryn
Publication year - 2008
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.22.1_supplement.824.1
Subject(s) - microbiology and biotechnology , cofilin , chemotaxis , arrestin , signal transducing adaptor protein , g protein coupled receptor , scaffold protein , signal transduction , wiskott–aldrich syndrome protein , internalization , biology , receptor , chemistry , actin cytoskeleton , cytoskeleton , cell , biochemistry
Beta‐arrestins are multifunctional adaptor proteins that mediate 7‐trans‐membrane (7TM)‐receptor signal desensitization and internalization, scaffolding of signaling molecules to specific cellular microdomains including those traditionally associated with chemotaxis. Protease‐activated‐receptor‐2 (PAR‐2) is a 7TM receptor that employs scaffolding function of beta‐arrestins for directed cell migration. Previously, we have shown that PAR‐2 elicits specific responses by differential activation of two pathways: classic Gαq/Ca 2+ and beta‐arrestin, both of which required for chemotaxis. Cell motility requires localized generation of free barbed ends, which can be achieved through regulation of the cofilin pathway. We show that localization cofilin, its phosphotase Chronophin (CIN), and its inhibitory kinase LIMK to the leading edge requires beta‐arrestins. Furthermore, beta‐arrestins, CIN and cofilin are essential for initial pseudopod extension in response to PAR‐2 activation. Both cofilin and CIN are found at the sites of newly generated barbed ends. Beta‐arrestin‐dependent localization of signaling molecules has significant implications for understanding of PAR‐2 induced chemotaxis during cancer metastasis, inflammation and wound healing. This work was supported by R01GM066151 (KAD)