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Steps to STIMulation

When ER calcium levels drop (right), STIM1 rapidly oligomerizes (yellow) and then translocates slowly to ER–PM junctions. MEYER/NAS

When ER calcium levels plummet, an ER membrane calcium sensor called STIM1 directly activates plasma membrane (PM) channels to top up the cell's calcium. Jen Liou, Tobias Meyer, and colleagues (Stanford University Medical School, Stanford, CA) have now uncovered the molecular steps of STIM1's pathway to the PM and show that those steps don't take STIM1 very far.

STIM1 sits in the ER membrane holding a calcium molecule in its luminal domain. When the ER loses calcium, STIM1 translocates along the ER membrane, ultimately aggregating at junctions between the PM and the ER. The details of these steps were unknown.

Using live cell imaging of fluorescent STIM1 fusion proteins, Liou et al. now show that, when ER calcium levels drop, STIM1's first step is to rapidly form oligomers. These oligomers then translocate and form visible aggregates. Aggregation, but not oligomerization, requires STIM1's polybasic tail—most likely for direct binding to the PM.

Formation of these aggregates was rapid, but STIM1 oligomers' translocation speed through the ER membrane was very slow. Therefore, the distance traveled to ER–PM junctions must be short. Reports have shown that STIM1 promotes calcium influx in localized regions of the PM. This is thought to spatially restrict activation of calcium-sensitive targets. STIM1's slow pace thus explains how this local action is achieved.

Reference:

Liou, N., et al. 2007. Proc. Natl. Acad. Sci. USA. doi:10.1073/pnas.0702866104.[Abstract/Free Full Text]

Ruth Williams

ruth.williams{at}rockefeller.edu

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This Article Full Text (PDF, 1144K) 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 Williams, R. Search for Related Content PubMed Articles by Williams, R. Social Bookmarking                            What's this?