“Regulation of Rho GTPase Activity by Adhesion Molecules, Mechanotransduction and other Factors”

Keith Burridge, PhD - University of North Carolina

Host: Tom Barker, PhD

Abstract:
Rho GTPases regulate many aspects of cell behavior, including the organization of the cytoskeleton, cell migration and cell adhesion, but also passage through the cell cycle, cell survival and gene expression. In my lab we are particularly interested in the roles of Rho proteins in cell-matrix and cell-cell adhesion. Not only do Rho proteins regulate adhesions but there is bidirectional signaling, with engagement of adhesion molecules regulating the activities of Rho proteins. Rho proteins are regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). In my talk I will describe assays that we have developed to identify active GEFs and GAPs in cell lysates. We have applied these techniques to identify GEFs for RhoA that become activated in response to integrin engagement. We have also been examining how RhoA is activated in response to mechanical tension applied to cell adhesion molecules. I will describe signaling pathways involved in mechanotransduction that mediate activation of specific GEFs. My lab is very interested in the adhesion and signaling events during leukocyte interactions with endothelial cells. In this context, we identified that RhoG is activated in and contributes to the endothelial cell response to leukocyte adhesion. Downstream from ICAM-1 engagement we discovered a RhoG GEF, SGEF, and have recently generated a knockout mouse for this exchange factor. This mouse is normal in most respects but exhibits an interesting phenotype in the context of atherosclerosis that I will describe.

The Bioengineering Seminar Series is a joint seminar series between IBB and the BME department. Seminars are held on Tuesdays or Thursdays between 11am-12pm in IBB room 1128 unless otherwise indicated.