"Calciosome," a cytoplasmic organelle: the inositol 1,4,5-trisphosphate-sensitive Ca2+ store of nonmuscle cells?
Calsequestrin (CS) is the protein responsible for the high-capacity, moderate affinity binding of Ca2+ within the terminal cisternae of the sarcoplasmic reticulum, believed up to now to be specific for striated muscle. The cells of two nonmuscle lines (HL-60 and PC12) and of two rat tissues (liver and pancreas) are shown here to express a protein that resembles CS in many respects (apparent mass and pH-dependent migration in NaDodSO4/PAGE; blue staining with StainsAll dye; Ca2+ binding ability) and is specifically recognized by affinity-purified antibodies against skeletal muscle CS. In these cells, the CS-like protein is shown by immunofluorescence and immunogold procedures to be localized within peculiar, heretofore unrecognized structures distributed throughout the cytoplasm. These structures appear to be discrete organelles, which we propose to be named "calciosomes." By cell fractionation (Percoll gradient and free-flow electrophoresis), the CS-like protein of HL-60 cells is shown to copurify with the markers of the inositol 1,4,5-trisphosphate (Ins-P3)-sensitive Ca2+ store, whereas the markers of other organelles (endoplasmic reticulum, Golgi complex, mitochondria, endosomes) and of the plasma membrane do not. Calciosome might thus be the intracellular target of Ins-P3--i.e., the source of the Ca2+ redistributed to the cytosol following receptor-triggered generation of the messenger.
Volpe
P
P
Consiglio Nazionale delle Ricerce Center for Muscle Biology and Physiopathology and of Biomembranes, University of Padova, Italy.
Krause
K H
KH
Hashimoto
S
S
Zorzato
F
F
Pozzan
T
T
Meldolesi
J
J
Lew
D P
DP
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D009940:Organoids / Q000187:drug effects / Q000502:physiology*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure
D007295:Inositol Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium