Seminar

Phil Esempio of the Glover Group

Tuesday, April 11, 2017 - 12:00am

Graduate student Phil Esempio will be presenting

"Structural and Biophysical Models for Vinculin-Phospholipid Interactions"

on April 11, 2017 at 4:10 PM in Neville Hall, Room 3. 

Abstract Vinculin is an essential adaptor protein which mediates connections between the cellular cytoskeleton (specifically filamentous actin) and the plasma membrane in eukaryotic cells.  Vinculin plays a role in the regulation of focal adhesions, cellular adhesion and migration, wound healing, and cellular response to mechanical forces.  Decreased or complete loss of vinculin expression is observed in many disease states, including cancer, cardiovascular disease, and embryonic lethality.  Recent research into the mechanisms by which vinculin links filamentous actin to the membrane have shown that it binds to a specific phospholipid, phosphatidylinositol 4,5-biphosphate (PIP2), and that specific regions of the vinculin structure are responsible for these protein-lipid interactions.  In particular, a number of biophysical assays were used to demonstrate that areas within the C-terminus of vinculin are crucial for binding to PIP2, and that this binding is essential for the activation of vinculin, and thus the regulation of focal adhesions.  These interactions may prove essential for the elucidation of other protein/lipid interactions, and their role in numerous disease states.     References Chinthalapudi, K.; Patil, D. N.; Rangarajan, E. S.; Rader, C.; Izard, T., Lipid-Directed Vinculin Dimerization. Biochemistry 2015, 54 (17), 2758-2768. Dwivedi, M.; Winter, R., Binding of vinculin to lipid membranes in its inhibited and activated states. Biophys. J. 2016, 111 (7), 1444-1453. Thompson, P. M.; Ramachandran, S.; Case, L. B.; Tolbert, C. E.; Tandon, A.; Pershad, M.; Dokholyan, N. V.; Waterman, C. M.; Campbell, S. L., A Structural Model for Vinculin Insertion into PIP2-Containing Membranes and the Effect of Insertion on Vinculin Activation and Localization. Structure (Oxford, U. K.) 2017, 25 (2), 264-275. Otto, J. J., Vinculin. Cell Motil. Cytoskeleton 1990, 16 (1), 1-6. Ziegler, W. H.; Gingras, A. R.; Critchley, D. R.; Emsley, J., Integrin connections to the cytoskeleton through talin and vinculin. Biochem. Soc. Symp. 2008, 75 (Structure and Function in Cell Adhesion), 169-177. Izard, T.; Brown, D. T., Mechanisms and Functions of Vinculin Interactions with Phospholipids at Cell Adhesion Sites. J. Biol. Chem. 2016, 291 (6), 2548-2555. Kim, L. Y.; Thompson, P. M.; Lee, H. T.; Pershad, M.; Campbell, S. L.; Alushin, G. M., The Structural Basis of Actin Organization by Vinculin and Metavinculin. Journal of Molecular Biology 2016, 428 (1), 10-25.