Capital Cells: The American Society for Cell Biology, Washington, D.C., December 1–5, 2007

JCB • VOLUME 180 • NUMBER 4 • 2008 654 STIM1 (green) hooks the ER to microtubule plus ends (red). A KH M A N O VA / EL SE VI ER ER takes trip on microtubule tips T he ER membrane hitches a ride on the tips of microtubules, as revealed by Susana Montenegro Gouveia. Gouveia, Ilya Grigoriev, and Anna Akhmanova (Erasmus Medical Center, Rotterdam, Netherlands) are interested in the growing tips of microtubules and their protein binding partners. Many of these partners also associate with one particularly common tip-binding protein, called EB1. Gouveia thus used EB1 as bait to identify new plus end– binding proteins. One of the most abundant proteins she isolated was an ER transmembrane protein called STIM1, which is well-known for its role in calcium signaling. When ER calcium levels drop, ERbound STIM1 cuddles up to the plasma membrane. It then helps open channels in the plasma membrane that let in calcium, which then refi lls the ER stores. The fi nding that STIM1 fastens to microtubules might help explain how the ER membrane gets close enough to the plasma membrane for STIM1 to open the channels: the membrane rides on growing microtubules. Gouveia showed that high levels of STIM1 caused ER membrane tubules to extend, while STIM1 depletion inhibited their extension. The loss of ER calcium, which forces STIM1 molecules into immobile aggregates, separated STIM1 from microtubule tips. Thus, as for other tip-binding proteins, STIM1 must be able to diffuse freely to maintain tip association. In this case, however, the diffusion occurs within the ER membrane rather than in the cytoplasm. Whether STIM1-mediated pulling of the ER membrane is required for calcium signaling is not clear. At least in fi broblasts, the link between STIM1 and microtubules was not necessary for channel opening. But in larger cells such as neurons, in which the ER must stretch farther to reach the periphery, the STIM1 link might be more vital. NL