TRPC3 mediates T-cell receptor-dependent calcium entry in human T-lymphocytes.
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.
Philipp
Stephan
S
Institut für experimentelle und klinische Pharmakologie und Toxikologie and the Institut für Physiologie, Gebäude 58, Universität des Saarlandes, D-66421 Homburg/Saar, Germany. stephan.philipp@uniklinik-saarland.de
Strauss
Bettina
B
Hirnet
Daniela
D
Wissenbach
Ulrich
U
Mery
Laurence
L
Flockerzi
Veit
V
Hoth
Markus
M
D001464:Barium / Q000378:metabolism; D020013:Calcium Signaling; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D017136:Ion Transport / Q000187:drug effects; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D050052:TRPC Cation Channels; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D018076:DNA, Complementary; D007473:Ion Channels; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D001464:Barium; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate