Inositol 1, 4, 5-trisphosphate receptor interacts with the SNARE domain of syntaxin 1B

Inositol 1, 4, 5-trisphosphate receptors (IP(3)Rs) are intracellular ligand-gated Ca(2+) channels that mediate Ca(2+) release from the endoplasmic reticulum (ER) into the cytosol and function in diverse cellular processes including fertilization, muscle contraction, apoptosis, secretion, and synaptic plasticity. The Ca(2+) release activity of IP(3)Rs is tightly regulated by many factors including IP(3)R-binding proteins. We show that IP(3)Rs interact with syntaxin 1 (Syx1), a membrane trafficking protein that regulates various plasma-membrane ion channels including N-, P/Q, and L-type voltage-gated Ca(2+) channels, voltage-gated potassium channels, and an epithelial sodium channel. We found that a SNARE-domain of Syx1B, one of the two Syx1 isoforms, directly interacted with the type1 IP(3)R (IP(3)R1) internal coupling domain, a known modulator for channel opening. These results indicate that Syx1B is an IP(3)R-interacting protein and that its interaction may play a crucial role in regulating the channel activity of IP(3)Rs in Syx1B-expressing cells.