CaT1 contributes to the stores-operated calcium current in Jurkat T-lymphocytes

Jie Cui, Jin Song Bian, Anna Kagan, Thomas V. McDonald

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

T-lymphocyte activation requires sustained Ca2+ signaling dependent upon capacitative Ca2+ entry (CCE). The protein(s) that forms the stores-operated Ca2+ channel (SOCC) responsible for CCE has long been sought but has not been definitively identified. Members of the TRPV family (transient receptor potential superfamily-vanilloid receptor subfamily) of channel genes have been proposed to encode SOCCs responsible for CCE in non-excitable cells. Here we present evidence that a member of the TRPV group, CaT1, is involved in generating ICRAC, the CCE current that is necessary for T-cell activation. CaT1 is expressed in Jurkat T-lymphocytes. When overexpressed in Jurkat cells, CaT1 produces a Ca2+ entry current that mimics the endogenous ICARC in its dependence on external Ca2+, inactivation by elevated concentration of internal Ca2+, and pharmacological block by capsaicin. Overexpressed CaT1 is partially regulated by the release of internal Ca2+ stores via thapsigargin or receptor-mediated generation of inositol 1,4,5-trisphosphate. A pore-region mutant of CaT1, TRIA-CaT1, fails to carry Ca2+ currents and associates with co-expressed wild type CaT1 to functionally suppress permeation of Ca2+ ions. Expression of the TRIA-CaT1 mutant in Jurkat cells results in suppression of the endogenous ICRAC. Taken together these results indicate that CaT1 is the channel protein that contributes to T-lymphocyte SOCCs either alone or as a subunit in a heterogeneous channel complex.

Original languageEnglish (US)
Pages (from-to)47175-47183
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number49
DOIs
StatePublished - Dec 6 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'CaT1 contributes to the stores-operated calcium current in Jurkat T-lymphocytes'. Together they form a unique fingerprint.

  • Cite this