Regulation of B Cell Migration and Antigen Receptor Signaling By Lsc

Cell migration is accomplished by chemoattractant receptors signaling the spatially-restricted activation of rho gtpases. specifically, chemoattractant receptors signal via gai and downstream guanine nucleotide exchange factors (gefs), p-rex and pixa, to activate rac and cdc42 at the leading edge and ultimately leads to cellular protrusion. In contrast, chemoattractant receptor signaling by ga12/13 activate rhoa at the trailing edge and promote cytoskeletal contraction. however, the gef(s) that activate rhoa downstream of chemoattractant receptor and ga12/13 have not been identified. here our study showed that: (1) the activity of lsc is controlled by oligomerization, (2) lsc is a key rhogef that functions as an effector of ga12/13-associated chemoattractant receptors to activate rhoa at the trailing edge and regulate the release of integrin-mediated cell adhesion during cell migration. Besides controlling cell migration, chemoattractant receptor signaling has also been suggested to regulate lymphocyte antigen receptor signaling. our study further revealed that bcr signaling is regulated by lysophosphatidic acid, and the underlying molecular mechanisms of this regulation.