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STIMulating Ca²⁺ influx

STIM1 (red) in the ER approaches Orai1 (green) in the plasma membrane upon loss of ER Ca2+ stores (bottom).

An ER protein scoots around to a site next to the plasma membrane (PM) to trigger calcium signaling, as shown by Wu et al. (page 803) and Luik et al. (page 815).

Cytoplasmic Ca²⁺ signals often come in two waves—a burst from the ER followed by a longer influx of extracellular Ca²⁺ through the PM's Ca²⁺ release–activated Ca²⁺ (CRAC) channels. The influx is triggered by the depletion of ER Ca²⁺ stores, which is sensed by a transmembrane ER Ca²⁺ sensor called STIM1. The new results reveal how STIM1 conveys the Ca²⁺ drop all the way from the ER to the PM.

Wu et al. show that Ca²⁺ store depletion causes STIM1 to relocate to ER regions that are just 10-25 nm from the PM. STIM1 accumulates at these sites several seconds before CRAC channels open.

In the second report, Luik et al. show that store depletion causes a CRAC channel subunit called Orai1 to accumulate in the PM opposite STIM1 puncta. They also find that Ca²⁺ influx through CRAC channels is limited to a small percentage of the cell surface in the immediate vicinity of these STIM1-Orai1 units.

The localized Ca²⁺ entry may restrict downstream responses to those mediated by nearby Ca²⁺-sensitive proteins. All the membrane and protein movements involved offer plenty of regulatory opportunities to enhance or dampen channel opening.

With such little space between them, STIM1 might activate Orai1 through physical interactions, perhaps through their predicted facing coiled-coil domains, but activation by a diffusible factor is also possible. Physical contact between STIM1 and a PM protein might explain why Wu et al. found about 50% more ER–PM junctions after Ca²⁺ store depletion. The group is now trying to determine how STIM1 and Orai1 find each other at these ER–PM junctions.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Ca²⁺ store depletion causes STIM1 to accumulate in ER regions closely associated with the plasma membrane

Minnie M. Wu, JoAnn Buchanan, Riina M. Luik, and Richard S. Lewis
J. Cell Biol. 2006 174: 803-813. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 1789K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Articles Social Bookmarking                            What's this?