Lumen cues calcium release

Lumen cues calcium release alcium release from lumenal stores is sensitive to the redox state of the ER lumen, as shown by Takayasu Higo, Katsuhiko Mikoshiba (University of Tokyo, Japan), and colleagues. The group has identified the first ER lumenal protein that controls IP 3 -regulated calcium channels (IP 3 Rs). The opening of IP 3 Rs is tightly controlled by cytosolic conditions. Most scientists assume that conditions in the ER also regulate channel opening, but the evidence was minimal. To find any relevant regulators in the ER, the authors used a lumenal domain of IP 3 R1 to fish out binding proteins. They discovered ERp44, whose association with IP 3 R1 blocked IP 3 -induced calcium release. But the binding of ERp44 and IP 3 R1, and subsequent channel blockage, depended on several conditions. First, the association occurred at low calcium levels, as would be seen after ER calcium stores are depleted. Second, it required that the lumenal domain of the channel be in its reduced state, with free thiol groups. That ERp44 is sensitive to the redox state is not surprising— C