My research focuses on the regulation of cell shape, motility and division by the actin cytoskeleton. The molecular mechanisms regulating the recruitment of actin and actin-binding proteins to specific sites in the cell, their assembly into macromolecular structures and the disassembly of these structures are unknown. Elucidating the molecular controls regulating these processes remains one of the major challenges in cell biology.
During mitosis in eukaryotic cells, the interaction of actin and myosin II results in the formation of a contractile ring that divides the cell in two. Myosin II is essential for cytokinesis; however, little is known about the biochemical signals which recruit actin, myosin II and other actin-binding proteins to the contractile ring, and regulate its contractile activity. Phosphorylation of the regulatory light chain of myosin II at two sets of sites regulates its activity in vitro. My laboratory is investigating myosin II phosphorylation and function in vivo, and more specifically the localization and activity of myosin II during cell motility and cytokinesis.
In locomoting cells, actin filaments in the cell cortex are organized into isotropic networks by specific actin-binding proteins. This family of actin cross-linking proteins have a modular organization which consists of a common actin binding domain and a dimerization domain of variable length composed of either a-helical or b-sheet repeats. Deletion or reduced expression of individual family members causes specific defects in cell motility, suggesting that individual family members participate in specialized biological functions. My laboratory is investigating how the length of the dimerization domain (i.e. number of a-helical or b-sheet repeats) permits the formation of actin networks with specific mechanochemical properties, and thereby specifies biological function.
References
Bresnick, A.R., Wolff-Long, V.L., Baumann, O. and Pollard, T.D. 1995. Phosphorylation on Threonine-18 of the Regulatory Light Chain Dissociates the ATPase and Motor Properties of Smooth Muscle Myosin II. Biochemistry 34: 12576-12583.
Bresnick, A.R., Janmey, P.A. and Condeelis, J. 1991. Evidence That a 27 Residue Sequence is the Actin Binding Site of ABP-120. J. Biol. Chem. 266:12989-12993.
Bresnick A.R., Warren, V. and Condeelis, J. 1990. Identification of a Short Sequence Essential for Actin Binding by Dictyostelium ABP-120. J. Biol. Chem. 265:9236-9240.
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