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.
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D002448:Cell Adhesion; D002460:Cell Line; D021961:Cell Membrane Structures / Q000378:metabolism; D016764:Cell Polarity; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D020710:RGS Proteins / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors
C577231:Arhgef1 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins; D011518:Proto-Oncogene Proteins; D020710:RGS Proteins; D064067:Rho Guanine Nucleotide Exchange Factors