W. Xu et al., Calreticulin modulates capacitative Ca2+ influx by controlling the extent of inositol 1,4,5-trisphosphate-induced Ca2+ store depletion, J BIOL CHEM, 275(47), 2000, pp. 36676-36682
Calreticulin (CRT) is a highly conserved Ca2+-binding protein that resides
in the lumen of the endoplasmic reticulum (ER). We overexpressed CRT in Xen
opus oocytes to determine how it could modulate inositol 1,4-5-trisphosphat
e (InsP(3))-induced Ca2+ influx. Under conditions where it did not affect t
he spatially complex elevations in free cytosolic Ca2+ concentration ([Ca2](i)) due to InsP(3)-induced Ca2+ release, overexpressed CRT decreased by 4
6% the Ca2+-gated Cl- current due to Ca2+ influx. Deletion mutants revealed
that CRT requires its high capacity Ca2+-binding domain to reduce the elev
ations of [Ca2+](i), due to Ca2+ influx. This functional domain was also re
quired for CRT to attenuate the InsP(3)-induced decline in the free Ca2+ co
ncentration within the ER lumen ([Ca2+](ER)), as monitored with a "chameleo
n" indicator. Our data suggest that by buffering [Ca2+](ER) near resting le
vels, CRT may prevent InsP(3) from depleting the intracellular stores suffi
ciently to activate Ca2+ influx.