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Actin cytoskeleton and cell signalling


The actin cytoskeleton plays a central role in many fundamental cell functions such as cell motility (Pollard and Borisy 2003)*, endocytosis (Jeng and Welch 2001), phagocytosis (Castellano and others 2001) and cytokinesis (Pollard and others 1990). The rem odelling of the actin cytoskeleton is controlled by multiple signalling pathways. The in vivo signalling activity of GTP-binding proteins ol the Rho subfamily requires numerous effectors, many of which are involved in regulating the reorganisation of the a ctin cytoskeleton (Bishop and Hall 2000). Recent results provided insights into the structure of one of these effectors, the Arp2/3 complex (Robinson and others 2001; Volkmann and others 2001). Formons, downstream effectors of Rho proteins, have multi-doma in structure involving FH1, FH2, FH3, auto-regulatory and Rho protein binding domains. For the S. cerevisiae formin, Bnilp, it has been shown that a construct of the FH1-FH2 region nucleates unbranched actin filaments in vitro independently of the Arp2/3 c omplex (Pring and others 2003; Pruyne and others 2002; Sagot and others 2002). However, much less is known about the corresponding domains from mammalian formins. To elucidate the molecular mechanisms underlying the function of mDia proteins we will stud} different mammalian formin domains. We have the expression systems (E. Coli) for three mDia FH2 domains. Our first experiments showed that the FH2 domain of mDia3 actually blocked the polymerisation by buiding to the barbed end of actin filaments. This FH2 domain could bind to actin filaments in a 1:1 molar ratio and decreased the critical concentration of actin. To gain further insights we will characterise /'. the effect of formin domains on the actin polymerisation, ii. the interaction of formin domains with actin in the presence of actin-binding proteins (e.g. tropomyosin) and their possible competition, Hi. the possible interactions between formins and actin monomers, iv. the #

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Funding Scheme

ERG - Marie Curie actions-European Re-integration Grants


Szanto Kovacs J. U. 1/B