Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239

Lindsay, S. L. , Ramsey, S., Aitchison, M., Renné, T. and Evans, T. J. (2007) Modulation of lamellipodial structure and dynamics by NO-dependent phosphorylation of VASP Ser239. Journal of Cell Science, 120(17), pp. 3011-3021. (doi: 10.1242/jcs.003061) (PMID:17684063)

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The initial step in directed cell movement is lamellipodial protrusion, an action driven by actin polymerization. Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family proteins are key regulators of this actin polymerization and can control lamellipodial protrusion rate. Ena/VASP proteins are substrates for modification by cyclic-nucleotide-dependent protein kinases at a number of sites. Phosphorylation of Ser239 of VASP in vitro inhibits its anti-capping and filament-bundling activity but the effects of this modification on lamellipodial structure and function are unknown. To examine the functional effects of this modification in living cells, we studied VASP phosphorylation at Ser239 by nitric oxide (NO) stimulation of cGMP-dependent protein kinase. Using live cell imaging of primary cells transfected with GFP-VASP constructs, we found that NO produced rapid retraction of lamellipodia together with cell rounding that was dependent on guanylate cyclase and type II cGMP-dependent protein kinase. In cells expressing a mutant VASP (Ser239Ala) lacking the site preferentially phosphorylated by this kinase, NO had no effect. Phosphorylation of Ser239 of VASP results in loss of lamellipodial protrusions and cell rounding, and is a powerful means of controlling directed actin polymerization within lamellipodia.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Evans, Professor Tom and Lindsay, Dr Susan
Authors: Lindsay, S. L., Ramsey, S., Aitchison, M., Renné, T., and Evans, T. J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Cell Science
Publisher:Company of Biologists
ISSN (Online):1477-9137

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