title: Dynamic cortical actin remodeling by ERM proteins controls BCR microcluster organization and integrity.
abstract: Signaling microclusters are a common feature of lymphocyte activation. However, the mechanisms controlling the size and organization of these discrete structures are poorly understood. The Ezrin-Radixin-Moesin (ERM) proteins, which link plasma membrane proteins with the actin cytoskeleton and regulate the steady-state diffusion dynamics of the B cell receptor (BCR), are transiently dephosphorylated upon antigen receptor stimulation. In this study, we show that the ERM proteins ezrin and moesin influence the organization and integrity of BCR microclusters. BCR-driven inactivation of ERM proteins is accompanied by a temporary increase in BCR diffusion, followed by BCR immobilization. Disruption of ERM protein function using dominant-negative or constitutively active ezrin constructs or knockdown of ezrin and moesin expression quantitatively and qualitatively alters BCR microcluster formation, antigen aggregation, and downstream BCR signal transduction. Chemical inhibition of actin polymerization also altered the structure and integrity of BCR microclusters. Together, these findings highlight a crucial role for the cortical actin cytoskeleton during B cell spreading and microcluster formation and function.
authors.affiliation: Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, England, UK. bebhinn.treanor@cancer.org.uk
authors.forename: Bebhinn
authors.initials: B
authors.lastname: Treanor
authors.forename: David
authors.initials: D
authors.lastname: Depoil
authors.forename: Andreas
authors.initials: A
authors.lastname: Bruckbauer
authors.forename: Facundo D
authors.initials: FD
authors.lastname: Batista
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003599:Cytoskeleton / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D055785:Gene Knockdown Techniques; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation / Q000235:genetics / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D000099149:Ezrin
chemical_list: D000199:Actins; D000941:Antigens; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D011947:Receptors, Antigen, B-Cell; D000099149:Ezrin; C071058:moesin