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Sci. STKE, 28 November 2006
Vol. 2006, Issue 363, p. re15
The Inositol 1,4,5-Trisphosphate Receptor (IP3R) and Its Regulators: Sometimes Good and Sometimes Bad Teamwork
Chi-un Choe1,2 and
Barbara E. Ehrlich1*
1Departments of Pharmacology and Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA. 2Institute for Neural Signal Transduction, Zentrum für Molekulare Neurobiologie Hamburg, University of Hamburg, 20251 Hamburg, Germany.
Gloss: Changes in the amount of calcium inside cells initiate many cellular events, including muscle contraction, hormone secretion, and cell growth. These changes can be modulated in time and space by the cell to tailor its response to the prevailing conditions. A major pathway used for the release of calcium from intracellular stores involves opening the inositol 1,4,5-trisphosphate receptor (IP3R), a calcium channel that is part of a signaling complex with multiple binding partners. This Review, which contains 2 tables, 6 figures, and 119 references, discusses the role of specific binding partners in regulating the function of the IP3R. These studies provide information on how these channels work and form the background for the investigation of disease-induced changes in calcium release channel function. The initiation of intracellular calcium signals can depend on factors as diverse as the nonuniform distribution of a binding partner in the lumen of the endoplasmic reticulum or the activation of a calcium-binding protein in the cytoplasm. Once calcium signals start, they can be transient, sustained, or oscillating; these temporal aspects of the signal are regulated by similarly diverse factors. Changes in intracellular calcium regulation occur in many diseases. As more and more new regulators of the IP3R are discovered, it will be important to understand the teamwork needed to regulate and modulate this complex system.