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.