PMID- 18362183 OWN - NLM STAT- MEDLINE DCOM- 20080429 LR - 20211020 IS - 1540-8140 (Electronic) IS - 0021-9525 (Print) IS - 0021-9525 (Linking) VI - 180 IP - 6 DP - 2008 Mar 24 TI - WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells. PG - 1245-60 LID - 10.1083/jcb.200708123 [doi] AB - We examined the role of the actin nucleation promoters neural Wiskott-Aldrich syndrome protein (N-WASP) and WAVE2 in cell protrusion in response to epidermal growth factor (EGF), a key regulator in carcinoma cell invasion. We found that WAVE2 knockdown (KD) suppresses lamellipod formation and increases filopod formation, whereas N-WASP KD has no effect. However, simultaneous KD of both proteins results in the formation of large jagged protrusions with lamellar properties and increased filopod formation. This suggests that another actin nucleation activity is at work in carcinoma cells in response to EGF. A mammalian Diaphanous-related formin, mDia1, localizes at the jagged protrusions in double KD cells. Constitutively active mDia1 recapitulated the phenotype, whereas inhibition of mDia1 blocked the formation of these protrusions. Increased RhoA activity, which stimulates mDia1 nucleation, was observed in the N-WASP/WAVE2 KD cells and was shown to be required for the N-WASP/WAVE2 KD phenotype. These data show that coordinate regulation between the WASP family and mDia proteins controls the balance between lamellar and lamellipodial protrusion activity. FAU - Sarmiento, Corina AU - Sarmiento C AD - Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA. csarmien@aecom.yu.edu FAU - Wang, Weigang AU - Wang W FAU - Dovas, Athanassios AU - Dovas A FAU - Yamaguchi, Hideki AU - Yamaguchi H FAU - Sidani, Mazen AU - Sidani M FAU - El-Sibai, Mirvat AU - El-Sibai M FAU - Desmarais, Vera AU - Desmarais V FAU - Holman, Holly A AU - Holman HA FAU - Kitchen, Susan AU - Kitchen S FAU - Backer, Jonathan M AU - Backer JM FAU - Alberts, Art AU - Alberts A FAU - Condeelis, John AU - Condeelis J LA - eng GR - R01 GM038511/GM/NIGMS NIH HHS/United States GR - GM38511/GM/NIGMS NIH HHS/United States GR - CA10023/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Biol JT - The Journal of cell biology JID - 0375356 RN - 0 (Carrier Proteins) RN - 0 (Diap1 protein, mouse) RN - 0 (Formins) RN - 0 (Wasl protein, rat) RN - 0 (Wiskott-Aldrich Syndrome Protein Family) RN - 0 (Wiskott-Aldrich Syndrome Protein, Neuronal) RN - 62229-50-9 (Epidermal Growth Factor) RN - EC 1.6.2.2 (Cyb5R3 protein, rat) RN - EC 1.6.2.2 (Cytochrome-B(5) Reductase) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - Actin Cytoskeleton/metabolism MH - Animals MH - Carcinoma/*metabolism MH - Carrier Proteins/genetics/*metabolism MH - Cell Line, Tumor MH - Cell Movement/drug effects/*physiology MH - Cell Surface Extensions/drug effects/*metabolism/ultrastructure MH - Cytochrome-B(5) Reductase/genetics/*metabolism MH - Down-Regulation/physiology MH - Epidermal Growth Factor/metabolism/pharmacology MH - Formins MH - Neoplasm Invasiveness/physiopathology MH - Neoplasms/*metabolism MH - Pseudopodia/drug effects/metabolism/ultrastructure MH - Rats MH - Wiskott-Aldrich Syndrome Protein Family/genetics/*metabolism MH - Wiskott-Aldrich Syndrome Protein, Neuronal/genetics/*metabolism MH - rhoA GTP-Binding Protein/metabolism PMC - PMC2290849 EDAT- 2008/03/26 09:00 MHDA- 2008/04/30 09:00 PMCR- 2008/09/24 CRDT- 2008/03/26 09:00 PHST- 2008/03/26 09:00 [pubmed] PHST- 2008/04/30 09:00 [medline] PHST- 2008/03/26 09:00 [entrez] PHST- 2008/09/24 00:00 [pmc-release] AID - jcb.200708123 [pii] AID - 200708123 [pii] AID - 10.1083/jcb.200708123 [doi] PST - ppublish SO - J Cell Biol. 2008 Mar 24;180(6):1245-60. doi: 10.1083/jcb.200708123.