Lsc activity is controlled by oligomerization and regulates integrin adhesion.

Lsc is a hematopoietic-restricted protein that functions as an effector of G alpha(12/13)-associated G-protein coupled receptors that activates RhoA. In the absence of Lsc leukocytes exhibit impaired migration and B lymphocytes inefficiently resolve integrin-mediated adhesion. Here, we demonstrate that Lsc exists physiologically in primary B lymphocytes as a large molecular weight complex resembling a homo-tetramer. Interfering with the assembly of this large molecular weight Lsc oligomer results in the activation of both Lsc functional activities and leads to cell rounding and inhibition of integrin-mediated adhesion. During cell migration on integrin ligands we find Lsc localizes predominantly toward the rear of migrating cells where we suggest it activates RhoA to resolve integin-mediated adhesion. Together these data demonstrate that Lsc regulates integrin-mediated adhesive events at the trailing edge of migrating cells.