Co-localization of calcium-modulating cyclophilin ligand with intracellular calcium pools

被引:44
作者
Holloway, MP
Bram, RJ
机构
[1] St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA
[2] St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA
[3] Univ Tennessee, Dept Pediat, Memphis, TN 38105 USA
关键词
D O I
10.1074/jbc.273.26.16346
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The calcium-modulating cyclophilin ligand (CAML) protein activates Ca2+ influx signaling when overexpressed in Jurkat T cells. Although CAML appears to directly participate in Ca2+-dependent signaling initiated by the transmembrane activator and CAML interactor cell surface receptor, its mechanism of action is unknown. To address this issue, we have determined its membrane topology, subcellular localization, and ability to mobilize intracellular Ca2+ pools. Fractionation of cell extracts on discontinuous sucrose gradients and indirect immunofluorescence indicate that CAML colocalizes with sarcoplasmic/endoplasmic reticulum calcium/ATPase-2 and calreticulin at membrane-bound cytosolic vesicles. Limited trypsin digests indicate that the hydrophilic NH2-terminal domain of CAML is directed toward the cytoplasm. Functionally, CAML overexpression was shown to deplete thapsigargin-sensitive intracellular Ca2+ pools. These data suggest that CAML may initiate Ca2+ signaling through activation of a capacitative Ca2+ influx pathway.
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页码:16346 / 16350
页数:5
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