"Calciosome," a cytoplasmic organelle: the inositol 1,4,5-trisphosphate-sensitive Ca2+ store of nonmuscle cells?

Abstract

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 afflinity-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-P--i.e., the source of the Ca2" redistributed to the cytosol following receptor-triggered generation of the messenger.

The Role of Formylpeptide Receptors, C5a Receptors, and Cytosolic-Free Calcium in Neutrophil Priming

“…Many mediators, including low concentrations of LTB 4 [25,26], 5-HETE [21], platelet activating factor [26,28], FMLP [21, 22,·24], and C5a (as shown here), plus cytokines such as granulocyte-This proposed priming mechanism is compatible with the observed priming requirements (table 2). Since priming also occurred in the absence of extracellular calcium, the small increase of intracellular free calcium arises via mobilization from intracellular pools [37]. This is also supported by the lack of priming after buffering [Ca2+]i with quin 2.…”

Two distinct Ca2+ storage and release sites in human neutrophils

“…These structures were shown to release Ca 2ϩ locally on adherence and with cross-linking stimuli [24], and were also mobile and moved to the leading edge during chemotaxis [25]. One possible identity for the peripheral Ca 2ϩ stores, identified by these older studies and by the data presented here, is calciosomes, small organelles that are widespread throughout neutrophils [26,27]. These organelles, which contain the necessary molecular characteristics for both Ca 2ϩ storage and release, are probably those which release local Ca 2ϩ in response to phagocytic events [28][29][30] and Fc receptor cross-linking [6,31,32].…”

Multiple Ca2+ signaling pathways converge on CaM kinase in PC12 cells

“…The IP3-sensitive stores in PC12 cells apl~ar to be localized throughout the ¢ytosol [12], where much of CaM kinase and many of its substrates are localized [2]. We show that at least three receptors in PCI2 ceils that couple to intracellular mobilization of Ca z+ (P2, M~, and B,, for ATP, aectylcholine, and bradykinin, resl~e-tively) all activate CaM kinase.…”