AJP - Cell Physiology, Vol 265, Issue 6 C1588-C1596, Copyright © 1993 by American Physiological Society

ARTICLES

Association of the hepatic IP3 receptor with the plasma membrane: relevance to mode of action

L. Feng and N. Kraus-Friedmann
Department of Physiology and Cell Biology, University of Texas Medical School at Houston 77225.

Studies were carried out to characterize the interaction between inositol 1,4,5-trisphosphate (IP3) receptors and the plasma membrane fraction. Extraction of the membranes with the nonionic detergents Nonidet P-40 and Triton X-100, followed by centrifugation at 100,000 g, resulted in the doubling of the IP3 receptor in the pellets, whereas no detectable binding was found in the supernatants. These data indicate that the detergents did not solubilize the receptor, that it remained associated with membrane particles, and that it is likely to be associated with the cytoskeleton. The cytoskeleton proteins actin, ankyrin, and spectrin were identified in the plasma membrane fraction. However, comparison of the amount of these proteins in different fractions of the detergent, or otherwise treated plasma membrane fractions, showed no direct correlation between the presence of any of these proteins in the plasma membrane fraction and their ability to bind [3H]IP3. This is in contrast to the brain and T-lymphoma cells in which the IP3 receptor is attached to ankyrin (L. Y. W. Bourguigon, H. Jin, N. Iida, N. R. Brandt, and S. H. Zhang. J. Biol. Chem. 268: 6477-6486, 1993; and S. K. Joseph and S. Samanta. J. Biol. Chem 268: 6477-6486, 1993). Thus the hepatic IP3 receptor, which is different from the brain receptor, might attach to the cytoskeleton by anchoring to a different protein. Because cytochalasin D treatment of livers diminishes the ability of IP3 to raise cytosolic free Ca2+ levels, the attachment of the IP3 receptor to the cytoskeleton seems to involve an association with microfilaments.

This article has been cited by other articles:

				A. Gysembergh, S. Lemaire, C. Piot, C. Sportouch, S. Richard, R. A. Kloner, and K. Przyklenk Pharmacological manipulation of Ins(1,4,5)P3 signaling mimics preconditioning in rabbit heart Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2458 - H2469. [Abstract] [Full Text] [PDF]

				E. Samain, H. Bouillier, C. Perret, M. Safar, and G. Dagher ANG II-induced Ca2+ increase in smooth muscle cells from SHR is regulated by actin and microtubule networks Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H834 - H841. [Abstract] [Full Text] [PDF]

				D. Tran, N. Stelly, T. Tordjmann, T. Durroux, M. N. Dufour, A. Forchioni, R. Seyer, M. Claret, and G. Guillon Distribution of Signaling Molecules Involved in Vasopressin-induced Ca2+ Mobilization in Rat Hepatocyte Multiplets J. Histochem. Cytochem., May 1, 1999; 47(5): 601 - 616. [Abstract] [Full Text]

				M. L. Cotrina, J. H.-C. Lin, and M. Nedergaard Cytoskeletal Assembly and ATP Release Regulate Astrocytic Calcium Signaling J. Neurosci., November 1, 1998; 18(21): 8794 - 8804. [Abstract] [Full Text] [PDF]