WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells

• DOI: 10.1083/jcb.200708123
• Publication Date: 2008-03-24T17:34:13Z
• Authors: Corina Sarmiento; Weigang Wang; Athanassios Dovas; Hideki Yamaguchi; Mazen Sidani; Mirvat El-Sibai; Vera DesMarais; Holly A. Holman; Susan Kitchen; Jonathan M. Backer; Art Alberts; John Condeelis
• Keywords: Formins; MDia1; Wiskott–Aldrich syndrome protein

We examined the role of actin nucleation promoters neural Wiskott-Aldrich syndrome protein (N-WASP) and WAVE2 in cell protrusion response to epidermal growth factor (EGF), a key regulator carcinoma invasion. found that knockdown (KD) suppresses lamellipod formation increases filopod formation, whereas N-WASP KD has no effect. However, simultaneous both proteins results large jagged protrusions with lamellar properties increased formation. This suggests another activity is at work cells EGF. A mammalian Diaphanous-related formin, mDia1, localizes double cells. Constitutively active mDia1 recapitulated phenotype, inhibition blocked these protrusions. Increased RhoA activity, which stimulates nucleation, was observed N-WASP/WAVE2 shown be required for phenotype. These data show coordinate regulation between WASP family mDia controls balance lamellipodial activity.