Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cytoskeletal Proteins / analysis
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Humans
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Immunoglobulin M / pharmacology
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Lymphocyte Activation
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Membrane Microdomains / chemistry
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Membrane Microdomains / metabolism*
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Mutation
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Phosphorylation
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Proteome / metabolism*
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Proteomics
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Receptors, Antigen, B-Cell / agonists
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Receptors, Antigen, B-Cell / metabolism*
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Recombinant Fusion Proteins / analysis
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Threonine / metabolism
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Tumor Cells, Cultured
Substances
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Cytoskeletal Proteins
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Immunoglobulin M
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Proteome
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Receptors, Antigen, B-Cell
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Recombinant Fusion Proteins
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ezrin
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Threonine