In cell signaling, calcium is king. The flux of calcium ions across cell membranes regulates cellular activities from muscle contraction to neuron firing to immune cell function. A talk I saw here at the Keystone symposium on the molecular basis for biological membrane organization in Big Sky, Montana, presented some significant steps forward in understanding the molecular pathway whereby the cell senses the depletion of calcium from stores in the endoplasmic reticulum and in order to allow the influx of fresh supplies.

Jen Liou, a Stanford biologist who I interviewed for a story last year about her discovery of the key signaling protein involved in store-operated calcium entry (SOC), presented new data on the pathway and told me that she plans to continue focusing on it as she seeks to set up her own lab.

Researchers still don't know how exactly the protein, called STIM1, interacts with and opens the calcium channel protein, Orai1, but Liou's presentation focused on her continued work on the functional dynamics of STIM proteins. She said that STIM1, which was though to be the main player in SOC, not only translocates from the endoplasmic reticulum to areas near the plasma membrane, but also oligomerizes prior to this translocation. Liou has found that this oligomerization may be key to STIM1's interaction with Orai1 or some unknown intermediate between the two proteins. Observing this phenomenon meant that Liou could identify a C-terminal amino acid motif that was likely binding STIM1 to phospholipids in the plasma membrane.

Liou also presented data that suggests a functional role for STIM2, a protein closely related to STIM1. She said STIM2 may be maintaining a stable calcium gradient prior to the dramatic influx mediated by STIM1.

As we chatted in front of her poster last night, I asked Liou how all the other potential players, such as the cell's cytoskeleton and lipids, might be affecting the dance between STIM1 and Orai1. She admitted that these aspects of the process are not yet well understood and that screening remains to be done to uncover other molecular players that may be functioning in SOC. "There is much more work to be done," Liou said, and she's planning on doing it. She's looking to set up her own lab (currently she works under Tobias Meyer at Stanford), which she will devote to elucidating the molecular intricacies of SOC.