Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 28 November 2006
Vol. 2006, Issue 363, p. re15
[DOI: 10.1126/stke.3632006re15]

REVIEWS

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.

Abstract: In both nonexcitable and excitable cells, the inositol 1,4,5-trisphosphate receptor (IP3R) is the primary cytosolic target responsible for the initiation of intracellular calcium (Ca2+) signaling. To fulfill this function, the IP3R depends on interaction with accessory subunits and regulatory proteins. These include proteins that reside in the lumen of the endoplasmic reticulum (ER), such as chromogranin A and B and ERp44, and cytosolic proteins, such as neuronal Ca2+ sensor 1, huntingtin, cytochrome c, IP3R-binding protein released with inositol 1,4,5-trisphosphate, Homer, and 4.1N. Specific interactions between these modulatory proteins and the IP3R have been described, making it clear that the controlled modulation of the IP3R by its binding partners is necessary for physiological cell regulation. The functional coupling of these modulators with the IP3R can control apoptosis, intracellular pH, the initiation and regulation of neuronal Ca2+ signaling, exocytosis, and gene expression. The pathophysiological relevance of IP3R modulation is apparent when the functional interaction of these proteins is enhanced or abolished by mutation or overexpression. The subsequent deregulation of the IP3R leads to pathological changes in Ca2+ signaling, signal initiation, the amplitude and frequency of Ca2+ signals, and the duration of the Ca2+ elevation. Consequences of this deregulation include abnormal growth and apoptosis. Complex regulation of Ca2+ signaling is required for the cell to live and function, and this difficult task can only be managed when the IP3R teams up and acts properly with its numerous binding partners.

*Corresponding author. E-mail, barbara.ehrlich{at}yale.edu

Citation: C.-u. Choe, B. E. Ehrlich, The Inositol 1,4,5-Trisphosphate Receptor (IP3R) and Its Regulators: Sometimes Good and Sometimes Bad Teamwork. Sci. STKE 2006, re15 (2006).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Transcranial magnetic stimulation and amyotrophic lateral sclerosis: pathophysiological insights.
S. Vucic, U. Ziemann, A. Eisen, M. Hallett, and M. C. Kiernan (2013)
J. Neurol. Neurosurg. Psychiatry 84, 1161-1170
   Abstract »    Full Text »    PDF »
Quantitative interactions between the A-type K+ current and inositol trisphosphate receptors regulate intraneuronal Ca2+ waves and synaptic plasticity.
S. Ashhad and R. Narayanan (2013)
J. Physiol. 591, 1645-1669
   Abstract »    Full Text »    PDF »
Re-evaluation of the Role of Calcium Homeostasis Endoplasmic Reticulum Protein (CHERP) in Cellular Calcium Signaling.
Y. Lin-Moshier, P. J. Sebastian, L. Higgins, N. D. Sampson, J. E. Hewitt, and J. S. Marchant (2013)
J. Biol. Chem. 288, 355-367
   Abstract »    Full Text »    PDF »
Calcium Channels in the Development, Maturation, and Function of Spermatozoa.
A. Darszon, T. Nishigaki, C. Beltran, and C. L. Trevino (2011)
Physiol Rev 91, 1305-1355
   Abstract »    Full Text »    PDF »
Chromogranin B in Heart Failure: A Putative Cardiac Biomarker Expressed in the Failing Myocardium.
H. Rosjo, C. Husberg, M. B. Dahl, M. Stridsberg, I. Sjaastad, A. V. Finsen, C. R. Carlson, E. Oie, T. Omland, and G. Christensen (2010)
Circ Heart Fail 3, 503-511
   Abstract »    Full Text »    PDF »
Distinct Domains within PSD-95 Mediate Synaptic Incorporation, Stabilization, and Activity-Dependent Trafficking.
J. F. Sturgill, P. Steiner, B. L. Czervionke, and B. L. Sabatini (2009)
J. Neurosci. 29, 12845-12854
   Abstract »    Full Text »    PDF »
Axonal mRNA in Uninjured and Regenerating Cortical Mammalian Axons.
A. M. Taylor, N. C. Berchtold, V. M. Perreau, C. H. Tu, N. Li Jeon, and C. W. Cotman (2009)
J. Neurosci. 29, 4697-4707
   Abstract »    Full Text »    PDF »
Calcium, Calpains, and Cardiac Hypertrophy: A New Link.
F. M. Heidrich and B. E. Ehrlich (2009)
Circ. Res. 104, e19-e20
   Full Text »    PDF »
Chromogranin B Regulates Calcium Signaling, Nuclear Factor {kappa}B Activity, and Brain Natriuretic Peptide Production in Cardiomyocytes.
F. M. Heidrich, K. Zhang, M. Estrada, Y. Huang, F. J. Giordano, and B. E. Ehrlich (2008)
Circ. Res. 102, 1230-1238
   Abstract »    Full Text »    PDF »
Phosphorylation of inositol 1,4,5-trisphosphate receptors by protein kinase B/Akt inhibits Ca2+ release and apoptosis.
T. Szado, V. Vanderheyden, J. B. Parys, H. De Smedt, K. Rietdorf, L. Kotelevets, E. Chastre, F. Khan, U. Landegren, O. Soderberg, et al. (2008)
PNAS 105, 2427-2432
   Abstract »    Full Text »    PDF »
The Inositol 1,4,5-Trisphosphate Receptor Is Required to Signal Autophagic Cell Death.
D. Lam, A. Kosta, M.-F. Luciani, and P. Golstein (2008)
Mol. Biol. Cell 19, 691-700
   Abstract »    Full Text »    PDF »
Regulation of the Inositol 1,4,5-Trisphosphate Receptor Type I by O-GlcNAc Glycosylation.
J. Rengifo, C. J. Gibson, E. Winkler, T. Collin, and B. E. Ehrlich (2007)
J. Neurosci. 27, 13813-13821
   Abstract »    Full Text »    PDF »
Bcl-2 Blocks Accretion or Depletion of Stored Calcium but Has No Effect on the Redistribution of IP3 Receptor I Mediated by Glycoprotein E of Herpes Simplex Virus 1.
M. Kalamvoki and B. Roizman (2007)
J. Virol. 81, 6316-6325
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882