Phosphorylation of WAVE2 by MAP kinases regulates persistent cell migration and polarity.
The WAVE family of proteins has long been implicated in the stimulus-dependent generation of lamellipodia at the leading edge of migrating cells, with WAVE2 in particular implicated in the formation of peripheral ruffles and chemotactic migration. However, the lack of direct visualisation of cell migration in WAVE2 mutants or knockdowns has made defining the mechanisms of WAVE2 regulation during cell migration difficult. We have characterised three MAP kinase phosphorylation sites within WAVE2 and analysed fibroblast behaviour in a scratch-wound model following introduction of transgenes encoding phospho-defective WAVE2. The cells exhibited an increase in migration speed, a decrease in the persistence of migration, and disruption of polarisation of the Golgi apparatus. All these effects could be mimicked by acute knockdown of endogenous WAVE2 expression with RNAi, indicating that phosphorylation of WAVE2 by MAP kinases regulates cell polarity during migration.
Danson
Christopher M
CM
Department of Biochemistry, Faculty of Medical and Veterinary Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK.
Pocha
Shirin M
SM
Bloomberg
Graham B
GB
Cory
Giles O
GO
D000818:Animals; D019556:COS Cells; D002465:Cell Movement; D016764:Cell Polarity; D002522:Chlorocebus aethiops; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D019076:Transgenes; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000737:chemistry / Q000378:metabolism*
D034741:RNA, Small Interfering; C492303:Wasf2 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family; D049452:Green Fluorescent Proteins; D020928:Mitogen-Activated Protein Kinases