PMID- 21482698 OWN - NLM STAT- MEDLINE DCOM- 20110718 LR - 20211020 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 208 IP - 5 DP - 2011 May 9 TI - Dynamic cortical actin remodeling by ERM proteins controls BCR microcluster organization and integrity. PG - 1055-68 LID - 10.1084/jem.20101125 [doi] AB - 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. FAU - Treanor, Bebhinn AU - Treanor B AD - Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, England, UK. bebhinn.treanor@cancer.org.uk FAU - Depoil, David AU - Depoil D FAU - Bruckbauer, Andreas AU - Bruckbauer A FAU - Batista, Facundo D AU - Batista FD LA - eng GR - Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110411 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Actins) RN - 0 (Antigens) RN - 0 (Cytoskeletal Proteins) RN - 0 (Microfilament Proteins) RN - 0 (Receptors, Antigen, B-Cell) RN - 0 (ezrin) RN - 144131-77-1 (moesin) SB - IM MH - Actins/genetics/*immunology/metabolism MH - Animals MH - Antigens/genetics/immunology MH - B-Lymphocytes/*immunology/metabolism MH - Cytoskeletal Proteins/genetics/*immunology/metabolism MH - Cytoskeleton/genetics/immunology/metabolism MH - Gene Expression Regulation/genetics/immunology MH - Gene Knockdown Techniques MH - Lymphocyte Activation/genetics/*immunology MH - Mice MH - Mice, Knockout MH - Microfilament Proteins/genetics/*immunology/metabolism MH - Phosphorylation/genetics/immunology MH - Receptors, Antigen, B-Cell/genetics/*immunology/metabolism MH - Signal Transduction/genetics/*immunology PMC - PMC3092358 EDAT- 2011/04/13 06:00 MHDA- 2011/07/19 06:00 PMCR- 2011/11/09 CRDT- 2011/04/13 06:00 PHST- 2011/04/13 06:00 [entrez] PHST- 2011/04/13 06:00 [pubmed] PHST- 2011/07/19 06:00 [medline] PHST- 2011/11/09 00:00 [pmc-release] AID - jem.20101125 [pii] AID - 20101125 [pii] AID - 10.1084/jem.20101125 [doi] PST - ppublish SO - J Exp Med. 2011 May 9;208(5):1055-68. doi: 10.1084/jem.20101125. Epub 2011 Apr 11.