Proteomics Analysis of the Ezrin Interactome in B Cells Reveals a Novel Association with Myo18aα

The molecular regulation of recruitment and assembly of signalosomes near the B cell receptor (BCR) is poorly understood. We have previously demonstrated a role for the ERM family protein ezrin in regulating antigen-dependent lipid raft coalescence in B cells. In this study, we addressed the possibility that ezrin may collaborate with other adaptor proteins to regulate signalosome dynamics at the membrane. Using mass spectrometry-based proteomics analysis, we identified Myo18a alpha as a novel binding partner of ezrin. Myo18a alpha is an attractive candidate as it has several protein-protein interaction domains and an intrinsic motor activity. The expression of Myo18a alpha varied during B cell development in the bone marrow and in mature B cell subsets suggesting functional differences. Interestingly, BCR stimulation increased the association between ezrin and Myo18a alpha, and induced co-segregation of Myo18a alpha with the BCR and phosphotyrosine containing proteins. Our data raise an intriguing possibility that the Myo18a alpha/ezrin complex may facilitate BCR-mediated signaling by recruiting signaling proteins that are in close proximity of the antigen receptor. Our study is not only significant with respect to understanding the molecular regulation of BCR signaling but also provides a broader basis for understanding the mechanism of action of ezrin in other cellular systems.