Calcium signalling mechanisms in endoplasmic reticulum activated by inositol 1,4,5-trisphosphate and GTP.
Ca2+ signals are known to mediate an array of cellular functions including secretion, contraction, and conductivity changes. In spite of the obvious role of Ca2+ in signalling, the control of Ca2+ within cells is known to be a complex phenomenon involving a number of distinct active and passive transport systems functioning within different organelles. Inositol 1,4,5-trisphosphate (IP3) is now established as a central mediator of Ca2+ mobilization, and the endoplasmic reticulum (ER) has been considered to be the site of action of IP3. However, this role has been ascribed almost by default to the ER, based on the knowledge that IP3 functions to release Ca2+ from an intracellular, nonmitochondrial, Ca2+-pumping organelle. Our interest has been to ascertain by what mechanism IP3 activates Ca2+ movements, at what intracellular locations it functions, and how the size and replenishment of the IP3-sensitive Ca2+ pool occurs. During the course of such studies, another mechanism inducing profound movements of Ca2+ within cells was identified. This process is activated by a highly sensitive and specific guanine nucleotide regulatory mechanism, which, while inducing fluxes of Ca2+ that resemble the action of IP3 under certain conditions, has now been determined to involve a quite distinct mechanism. The characteristics of this mechanism are described below. Although involving a very different Ca2+ translocation process to that activated by IP3, several important conclusions have been drawn on the relationship between IP3- and GTP-activated Ca2+ movements leading us to believe that the latter may have a regulatory role in controlling the size and/or entry of Ca2+ into the IP3-sensitive Ca2+ pool.
Gill
D L
DL
Department of Biological Chemistry, University of Maryland School of Medicine, Baltimore.
Ghosh
T K
TK
Mullaney
J M
JM
D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D015398:Signal Transduction; D013403:Sugar Phosphates / Q000378:metabolism*; D013696:Temperature
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D006493:Heparin; D002118:Calcium