Molecular mechanisms of function and regulation of the actin cytoskeleton
The actin cytoskeleton underlies nearly every fundamental cellular activity including determination and maintenance of cell shape. intracellular architecture and tissue formation, transport of organelles within the cell and movement of the cells themselves, as well as intracellular and cellular signaling. Long-standing, and continuing biochemical and biophysical research has come together with more recent cellular and genetic experiments to show that tropomyosin is a major cellular regulator of actin filament stability and binding of other proteins to actin that modulate its function. Our goal is to understand the molecular mechanisms underlying the regulation of actin filament contractile and motile function. Research projects range from biophysics and biochemistry to cell biology: Current work includes (1) determination of structures of functional fragments of tropomyosin and tropomyosin binding proteins at atomic resolution using heteronuclear NMR (the work of Dr. Norma Greenfield), (2) analysis of the importance of flexibility for function in coiled coil cytoskeletal proteins, (3) study of the regulation of actin dynamics by proteins that bind to actin including tropomyosin, tropomodulin, and the Arp2/3 complex, and (4) experiments to understand the function of specific tropomyosin isoforms in cells.