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

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 I_CRAC, 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 I_CARC 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 I_CRAC. 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.