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Regulation of cellular actin dynamics by FMNL subfamily formins

Fachliche Zuordnung Zellbiologie
Förderung Förderung von 2010 bis 2017
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 170444734
 
Cell migration is initiated by protrusion of cellular projections at the cell front, such as lamellipodia and filopodia. These structures are built by polymerising actin filaments, the nucleation of which is catalyzed by diverse molecular machines, for instance members of the formin family of actin nucleators, comprising 15 members in mammals. Some formins such as mDia1 or mDia2 have been shown to localize to and/or trigger the formation of filopodia, but neither of these appears essential for the process. In a search for potential new filopodial regulators, we have begun to analyse FMNL2 (also called FRL3), a widely expressed member of a subgroup of formins that have previously been implicated in the protrusion of both lamellipodia and filopodia. Preliminary work demonstrates that FMNL2 bind Cdc42 and Rac1 small GTPases, and strongly accumulates at the tips of protruding lamellipodia and filopodia. This project aims at elucidating the precise function of FMNL2 in the formation of cellular protrusions and cell migration. Furthermore, we will analyse the potential of FMNL2 to nucleate and/or elongate actin filaments in vitro, and characterise its regulation by Rho-GTPases and other interaction partners both in vitro and in vivo.
DFG-Verfahren Schwerpunktprogramme
 
 

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