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J. Biol. Chem., Vol. 283, Issue 2, 751-755, January 11, 2008

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Counting Functional Inositol 1,4,5-Trisphosphate Receptors into the Plasma Membrane^*

From the Department of Pharmacology, Tennis Court Road, University of Cambridge, Cambridge CB2 1PD, United Kingdom

Inositol 1,4,5-trisphosphate receptors (IP₃R) within the endoplasmic reticulum mediate release of Ca²⁺ from intracellular stores. Different channels usually mediate Ca²⁺ entry across the plasma membrane. In B lymphocytes and a cell line derived from them (DT40 cells), very few functional IP₃R(2/cell) are invariably expressed in the plasma membrane, where they mediate about half the Ca²⁺ entry evoked by activation of the B-cell receptor. We show that cells reliably count 2 functional IP₃R into the plasma membrane even when their conductance and ability to bind IP₃ are massively attenuated. We conclude that very small numbers of functional IP₃R can be reliably counted into a specific membrane compartment in the absence of feedback signals from the active protein.

Received for publication, August 20, 2007 , and in revised form, November 12, 2007.

^* This work was supported by the Wellcome Trust. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Methods and references, supplemental Figs. S1 and S2, and supplemental Table S1.

¹ To whom correspondence should be addressed. Tel. 44-1223-334058; E-mail: cwt1000{at}cam.ac.uk.

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