RESUMO
The mouse TRPV6 gene is localized on chromosome 6 and extends over 15.66kb. The encoded protein comprises 727 amino acid residues with a calculated relative molecular mass of 83,210Da. TRPV6 is glycosylated and both variants, the glycosylated and the de-glycosylated proteins, are recognized by various polyclonal and monoclonal antibodies, which were raised against TRPV6. Like human TRPV6, mouse TRPV6 binds calmodulin in the presence, but not in the absence of Ca2+. TRPV6 is abundantly expressed in mouse pancreas and placenta, and to a much lesser extend in mouse stomach and kidney. No transcript expression was detected in poly(A)+RNA isolated from heart, brain, intestine, esophagus or aortic endothelial cells.
Assuntos
Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Cálcio/metabolismo , DNA Complementar/química , Placenta/química , Sequência de Aminoácidos , Animais , Células CHO , Canais de Cálcio/imunologia , Calmodulina/metabolismo , Células Cultivadas , Clonagem Molecular , Cricetinae , DNA Complementar/genética , Glicosilação , Humanos , Camundongos , Dados de Sequência Molecular , Fragmentos de Peptídeos/imunologia , Poli A/genética , Coelhos , Homologia de Sequência de Aminoácidos , Canais de Cátion TRPV , Distribuição TecidualRESUMO
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.