TY - JOUR
T1 - CaT1 contributes to the stores-operated calcium current in Jurkat T-lymphocytes
AU - Cui, Jie
AU - Bian, Jin Song
AU - Kagan, Anna
AU - McDonald, Thomas V.
PY - 2002/12/6
Y1 - 2002/12/6
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M205870200
DO - 10.1074/jbc.M205870200
M3 - Article
C2 - 12361955
AN - SCOPUS:0037032988
SN - 0021-9258
VL - 277
SP - 47175
EP - 47183
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 49
ER -