Abstract
Stimulation of the T-cell receptor (TCR) activates Ca2+ entry across the plasma membrane, which is a key triggering event for the T-cell-associated immune response. We show that TRPC3 channels are important for the TCR-dependent Ca2+ entry pathway. The TRPC3 gene was found to be damaged in human T-cell mutants defective in Ca2+ influx. Mutations of the TRPC3 gene were accompanied by changes of TRPC3 gene expression. Introduction of the complete human TRPC3 cDNA into those mutants rescued Ca2+ currents as well as TCR-dependent Ca2+ signals. Our data provide the initial step toward understanding the molecular nature of endogenous Ca2+ channels participating in T-cell activation and put forward TRPC3 as a new target for modulating the immune response.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Barium / metabolism
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Calcium Signaling*
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DNA, Complementary / genetics
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Gene Expression
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Genotype
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Humans
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Inositol 1,4,5-Trisphosphate / metabolism
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Ion Channels / genetics
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Ion Channels / metabolism*
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Ion Transport / drug effects
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Jurkat Cells
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Lymphocyte Activation
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Mutation
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Receptors, Antigen, T-Cell / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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TRPC Cation Channels
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Thapsigargin / pharmacology
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Transfection
Substances
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DNA, Complementary
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Ion Channels
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Receptors, Antigen, T-Cell
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Recombinant Proteins
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TRPC Cation Channels
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TRPC3 cation channel
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Barium
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Thapsigargin
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Inositol 1,4,5-Trisphosphate