期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 22, 页码 9301-9306出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0702866104
关键词
Ca2+ release-activated Ca2+; fluorescence recovery after photobleaching; FRET; store-operated Ca2+ influx
资金
- NIGMS NIH HHS [GM 030179, R37 GM030179, R01 GM030179] Funding Source: Medline
Stromal interaction molecule 1 (STIM1) has recently been identified by our group and others as an endoplasmic reticulum (ER) Ca2+ sensor that responds to ER Ca2+ store depletion and activates Ca2+ channels in the plasma membrane (PM). The molecular mechanism by which STIM1 transduces signals from the ER lumen to the PM is not yet understood. Here we developed a live-cell FRET approach and show that STIM1 forms oligomers within 5 s after Ca2+ store depletion. These oligomers rapidly dissociated when ER Ca2+ stores were refilled. We further show that STIM1 formed oligomers before its translocation within the ER network to ER-PM junctions. A mutant STIM1 lacking the C-terminal polybasic PM-targeting motif oligomerized after Ca2+ store depletion but failed to form puncta at ER-PM junctions. Using fluorescence recovery after photobleaching measurements to monitor STIM1 mobility, we show that STIM1 oligomers translocate on average only 2 fcm to reach ER-PM junctions, arguing that STIM1 ER-to-PM signaling is a local process that is suitable for generating cytosolic Ca2+ gradients. Together, our live-cell measurements dissect the STIM1 ER-to-PM signaling relay into four sequential steps: (i) dissociation of Ca2+, (if) rapid oligomerization, (iii) spatially restricted translocation to nearby ER-PM junctions, and (iv) activation of PM Ca2+ channels.
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