title: Proteomics analysis of the ezrin interactome in B cells reveals a novel association with Myo18aα.
abstract: 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 Myo18aα as a novel binding partner of ezrin. Myo18aα is an attractive candidate as it has several protein-protein interaction domains and an intrinsic motor activity. The expression of Myo18aα 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 Myo18aα, and induced co-segregation of Myo18aα with the BCR and phosphotyrosine-containing proteins. Our data raise an intriguing possibility that the Myo18aα/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.
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: Ken
authors.initials: K
authors.lastname: Matsui
authors.forename: Neetha
authors.initials: N
authors.lastname: Parameswaran
authors.forename: Nayer
authors.initials: N
authors.lastname: Bagheri
authors.forename: Belinda
authors.initials: B
authors.lastname: Willard
authors.forename: Neetu
authors.initials: N
authors.lastname: Gupta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D009218:Myosins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D040901:Proteomics / Q000379:methods*; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000378:metabolism; D000099149:Ezrin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D009218:Myosins; D011947:Receptors, Antigen, B-Cell; D000099149:Ezrin; C407152:MYO18A protein, human