ERp44 (red) binds to the lumenal side of IP3R1 (green) to inhibit calcium release.
MIKOSHIBA/ELSEVIER
Calcium 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
3Rs).The opening of IP
3Rs 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
3R1 to fish out binding proteins. They discovered ERp44, whose association with IP
3R1 blocked IP
3-induced calcium release.
But the binding of ERp44 and IP3R1, and subsequent channel blockage, depended on...