Rac-mediated Stimulation of Phospholipase C?2 Amplifies B Cell Receptor-induced Calcium Signaling.

ABSTRACT: The Rho GTPase Rac is crucially involved in controlling multiple B cell functions, including those regulated by the B cell receptor (BCR) through increased cytosolic Ca(2+). The underlying molecular mechanisms and their relevance to the functions of intact B cells have thus far remained unknown. We have previously shown that the activity of phospholipase C?2 (PLC?2), a key constituent of the BCR signalosome, is stimulated by activated Rac through direct protein-protein interaction. Here, we use a Rac-resistant mutant of PLC?2 to functionally reconstitute cultured PLC?2-deficient DT40 B cells and to examine the effects of the Rac-PLC?2 interaction on BCR-mediated changes of intracellular Ca(2+) and regulation of Ca(2+)-regulated and nuclear-factor-of-activated-T-cell-regulated gene transcription at the level of single, intact B cells. The results show that the functional Rac-PLC?2 interaction causes marked increases in the following: (i) sensitivity of B cells to BCR ligation; (ii) BCR-mediated Ca(2+) release from intracellular stores; (iii) Ca(2+) entry from the extracellular compartment; and (iv) nuclear translocation of the Ca(2+)-regulated nuclear factor of activated T cells. Hence, Rac-mediated stimulation of PLC?2 activity serves to amplify B cell receptor-induced Ca(2+) signaling.

SUBMITTER: Walliser C 

PROVIDER: S-EPMC4498044 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature