Lipid rafts interaction of the ARID3A transcription factor with EZRIN and G-Actin regulates B cell receptor signaling

Abstract

ABSTRACTPreviously we demonstrated that the ARID3A transcription factor shuttles between the nucleus and the plasma membrane, where it localizes within lipid rafts. There it interacts with components of the B Cell Receptor (BCR) to reduce its ability to transmit downstream signaling. We demonstrate in this report that a direct component of ARID3A-regulated BCR signal strength is cortical Actin. ARID3A interacts with Actin exclusively within lipid rafts via the Actin binding protein EZRIN, which confines unstimulated BCRs within lipid rafts. BCR ligation discharges the ARID3A-EZRIN complex from lipid rafts allowing the BCR to initiate downstream signaling events. The ARID3A-EZRIN interaction occurs almost exclusively within unpolymerized G-Actin where EZRIN interacts with the multifunctional ARID3A REKLES domain. These observations provide a novel mechanism by which a transcription factor directly regulates BCR signaling.