Quantitative proteomic analysis of B cell lipid rafts reveals that ezrin regulates antigen receptor-mediated lipid raft dynamics.
Ligation of the B cell antigen receptor (BCR) with antigen induces lipid raft coalescence, a process that occurs after crosslinking of a variety of signaling receptors and is thought to potentiate cellular activation. To investigate lipid raft dynamics during BCR signaling, we quantitatively analyzed the B cell lipid raft proteome. BCR engagement induced dissociation of the adaptor protein ezrin from lipid rafts as well as threonine dephosphorylation of ezrin and its concomitant detachment from actin, indicating a transient uncoupling of lipid rafts from the actin cytoskeleton. Expression of constitutively active ezrin chimeras inhibited the BCR-induced coalescence of lipid rafts. Our data demonstrate that the release of ezrin from lipid rafts acts as a critical trigger that regulates lipid raft dynamics during BCR signaling.
Gupta
Neetu
N
Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA.
Wollscheid
Bernd
B
Watts
Julian D
JD
Scheer
Barbara
B
Aebersold
Ruedi
R
DeFranco
Anthony L
AL
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000494:pharmacology; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011947:Receptors, Antigen, B-Cell / Q000819:agonists / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D007075:Immunoglobulin M; D020543:Proteome; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D013912:Threonine; D000099149:Ezrin