Calreticulin inhibits repetitive intracellular Ca2+ waves.
Inositol 1,4,5-trisphosphate (IP3)-mediated calcium (Ca2+) signaling is subject to cytosolic and luminal regulatory mechanisms. In Xenopus oocytes, Ca(2+)-sensitive gating of the IP3 receptor (IP3R) produces repetitive waves of Ca2+ release. We examined the role of the luminal Ca(2+)-binding protein calreticulin (CRT) in IP3-mediated Ca2+ signaling by using Ca2+ wave activity as a sensitive Ca2+ release assay. Overexpression of CRT inhibited repetitive IP3-induced Ca2+ waves. Deletion mutagenesis demonstrated that CRT inhibition was mediated by the high affinity-low capacity Ca(2+)-binding domain, which contributes little to Ca2+ storage. This novel function of CRT in intracellular Ca2+ signaling may be regulated by Ca2+ occupancy of the high affinity binding site.
Camacho
P
P
Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Lechleiter
J D
JD
D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D001483:Base Sequence; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000502:physiology; D037282:Calreticulin; D007150:Immunohistochemistry; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D009865:Oocytes / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D012261:Ribonucleoproteins / Q000235:genetics / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D014982:Xenopus laevis
D001324:Autoantigens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D012261:Ribonucleoproteins; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium