ACTIN CYTOSKELETON · Actin cytoskeleton and cell signalling
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2004-01-01 → 2004-12-31
- EU contribution
- €40,000
- Participants
- 1
- Scheme
- ERG
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Results in brief
Final Activity Report Summary - ACTIN CYTOSKELETON (Actin cytoskeleton and cell signalling)
The major aims of this project were to provide financial support for young researchers reintegrating to their home country. In accordance with this aim, a substantial part of the support was spent establishing the appropriate environment for my group to carry out the research activities outlined in my proposal. These investments involved the purchase of chemicals, pipettes, plastic and glass wear, fluorescence and phophorescence cuvettes and numerous other consumables which are essential for the investigations. These investments greatly enhanced the available lab facilities, increased the efficiency of my group, and provided the essential conditions for the initiation of research activity after my return to Pécs from England. Scientific results due to the effective reintegration of the actin cytoskeleton group could start the research activities with relatively short delay. The studies involved in this period were of two kinds, studies in collaboration with international research groups (from Germany, England, Finland) and investigations by the group with no collaborations. In collaboration with Professor Alfred Wittinghofer's research group we determined the three dimensional structure of an fh2 formin fragment from a mammalian (mouse) source. The structure of the mdia1-fh2 was resolved and interpreted in the light of the biochemical results obtained in this project. This work appeared in Molecular Cell (2004, 565(1-3); 163) and was the first formin structure published. In the investigation of motor proteins we described the function and kinetic behaviour of single and double headed kinesins. The results were published in 2004. As a result of the initiation of the work in Hungary, a new project investigated the interactions between cyclic toxic hexapeptides phalloidin and jasplakinolide- with actin filaments. The observation clearly showed that both drugs have a substantial effect on the conformation of actin filaments, and the effect of jasplakinolide proved to be stronger than that of phalloidin. Our data also demonstrated that there are long range allosteric interactions along he actin filaments, suggesting that these interactions can play important role in vivo as information channels. The results were published in two articles.
Data: CORDIS, © European Union
Project objective
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 #
Original text from CORDIS.
Participants
- DEPARTMENT OF BIOPHYSICS · PECSCoordinatorCity levelHungary
Links
Data: CORDIS, © European Union