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Moreover, RNA interference (RNAi) approaches demonstrated that endogenous R-Ras contributed to cell spreading. These observations suggest that R-Ras regulates membrane protrusions through organization of the actin cytoskeleton. Our results suggest that phospholipase C\u03f5 (PLC\u03f5) is a novel R-Ras effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion, because R-Ras was co-precipitated with PLC\u03f5 and increased its activity. Knockdown of PLC\u03f5 with siRNA reduced the formation of the ruffling lamellipod in R-Ras cells. Consistent with this pathway, inhibitors of PLC activity, or chelating intracellular Ca2+ abolished the ability of R-Ras to promote membrane protrusions and spreading. Overall, these data suggest that R-Ras signaling regulates the organization of the actin cytoskeleton to sustain membrane protrusion through the activity of PLC\u03f5.<\/jats:p>","DOI":"10.1242\/jcs.02835","type":"journal-article","created":{"date-parts":[[2006,3,15]],"date-time":"2006-03-15T02:33:27Z","timestamp":1142390007000},"page":"1307-1319","source":"Crossref","is-referenced-by-count":69,"title":["The small GTPase R-Ras regulates organization of actin and drives membrane protrusions through the activity of PLC\u03f5"],"prefix":"10.1242","volume":"119","author":[{"given":"Aude S.","family":"Ada-Nguema","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Xenias","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Sheetz","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Keely","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042519485036800_REF1","doi-asserted-by":"crossref","unstructured":"Arora, P. 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