Mobile IP 3 Receptors

Abstract

Inositol trisphosphate (IP 3 ) receptors (IP 3 Rs) are located on internal membranes, most commonly the endoplasmic reticulum (ER) or sarcoplasmic reticulum, and are responsible for contributing to calcium signals that are generated in response to external signals that result in the production of the second messenger IP 3 . Calcium signals are not uniform, but rather show complex spatial and temporal dynamics. Vermassen et al. used confocal microscopy to show that in cells natively expressing the IP 3 R1 and IP 3 R3 isoforms, the IP 3 R1 redistributed from the perinuclear region to a more uniform distribution within the cell in response to prolonged stimulation of the vasopressin receptor. Redistribution of the IP 3 R1s also occurred in response to phospholipase C (PLC) or protein kinase C (PKC) activation, application of a cell permeable IP 3 ester, and emptying of the ER calcium stores with drugs that block the ER Ca 2+ pump. The microtubular cytoskeleton is a target of PKC. Indeed, the redistribution of IP3R1s was blocked by microtubule-stabilizing drugs, and the microtubular cytoskeleton underwent a morphological change in response to prolonged vasopressin receptor activation. Because IP3Rs are ER-resident proteins, the authors investigated the distribution of several ER marker proteins and determined that, generally, the ER structure and distribution was unchanged by conditions that redistribute IP 3 R1. Only the Ca 2+ pump showed a similar perinuclear distribution in unstimulated cells and a more widely distributed pattern after stimulation, like that seen for IP 3 R1. Experiments with brefeldin A and temperature suggested that vesicle trafficking, instead of gross ER reorganization, was responsible for the redistribution of these proteins involved in calcium signaling. E. Vermassen, K. Van Acker, W. G. Annaert, B. Himpens, G. Callewaert, L. Missiaen, H. De Smedt, J. B. Parys, Microtubule-dependent redistribution of the type-1 inositol 1,4,5-trisphosphate receptor in A7r5 smooth muscle cells. J. Cell Sci. 116 , 1269-1277 (2003). [Abstract] [Full Text]