Analysis of IP3 receptors in and out of cells

Biochim Biophys Acta. 2012 Aug;1820(8):1214-27. doi: 10.1016/j.bbagen.2011.10.004. Epub 2011 Oct 14.

Abstract

Background: Inositol 1,4,5-trisphosphate receptors (IP3R) are expressed in almost all animal cells. Three mammalian genes encode closely related IP3R subunits, which assemble into homo- or hetero-tetramers to form intracellular Ca2+ channels.

Scope of the review: In this brief review, we first consider a variety of complementary methods that allow the links between IP3 binding and channel gating to be defined. How does IP3 binding to the IP3-binding core in each IP3R subunit cause opening of a cation-selective pore formed by residues towards the C-terminal? We then describe methods that allow IP3, Ca2+ signals and IP3R mobility to be examined in intact cells. A final section briefly considers genetic analyses of IP3R signalling.

Major conclusions: All IP3R are regulated by both IP3 and Ca2+. This allows them to initiate and regeneratively propagate intracellular Ca2+ signals. The elementary Ca2+ release events evoked by IP3 in intact cells are mediated by very small numbers of active IP3R and the Ca2+-mediated interactions between them. The spatial organization of these Ca2+ signals and their stochastic dependence on so few IP3Rs highlight the need for methods that allow the spatial organization of IP3R signalling to be addressed with single-molecule resolution.

General significance: A variety of complementary methods provide insight into the structural basis of IP3R activation and the contributions of IP3-evoked Ca2+ signals to cellular physiology. This article is part of a Special Issue entitled Biochemical, biophysical and genetic approaches to intracellular calcium signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Calcium Signaling
  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol 1,4,5-Trisphosphate / physiology
  • Inositol 1,4,5-Trisphosphate Receptors / chemistry
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism*
  • Membrane Potentials
  • Microscopy, Fluorescence
  • Patch-Clamp Techniques
  • Protein Transport
  • Single-Cell Analysis

Substances

  • Inositol 1,4,5-Trisphosphate Receptors
  • Inositol 1,4,5-Trisphosphate