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Publication : Localized RhoA activation as a requirement for the induction of membrane ruffling.

First Author  Kurokawa K Year  2005
Journal  Mol Biol Cell Volume  16
Issue  9 Pages  4294-303
PubMed ID  15987744 Mgi Jnum  J:103916
Mgi Id  MGI:3610863 Doi  10.1091/mbc.E04-12-1076
Citation  Kurokawa K, et al. (2005) Localized RhoA activation as a requirement for the induction of membrane ruffling. Mol Biol Cell 16(9):4294-303
abstractText  We examined the spatio-temporal activity of RhoA in migrating cells and growth factor-stimulated cells by using probes based on the principle of fluorescence resonance energy transfer. In HeLa cells migrating at a low cell density, RhoA was activated both at the contractile tail and at the leading edge. However, RhoA was activated only at the leading edge in MDCK cells migrating as a monolayer sheet. In growth factor-stimulated Cos1 and NIH3T3 cells, the activity of RhoA was greatly decreased at the plasma membrane, but remained high at the membrane ruffles in nascent lamellipodia. These observations are in agreement with the proposed role played by RhoA in stress fiber formation, but they also implicated RhoA in the regulation of membrane ruffling, the induction of which is a typical phenotype of activated Rac. In agreement with this view, dominant negative RhoA was found to inhibit membrane ruffling induced by active Rac. Furthermore, we found that Cdc42 activity was also required for high RhoA activity in membrane ruffles. Finally, we found that mDia1, but not ROCK, was stably associated with membrane ruffles. In conclusion, these results suggested that RhoA cooperates with Rac1 and Cdc42 to induce membrane ruffles via the recruitment of mDia.
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