Themes and Variations in Endoplasmic Reticulum Calcium Release Channels: Structure and Function

Abstract

Calcium (Ca²⁺) release from the sarco/endoplasmic reticulum stores generates vital regulatory signals in eukaryotes. The two major groups of Ca²⁺ release channels include the ubiquitously expressed inositol 1,4,5-trisphosphate receptors (IP₃Rs) and the ryanodine receptors (RyRs). This review focuses on recently reported structural findings on the N-terminal regions of IP₃Rs and RyRs and their arrangement into full-length tetrameric channels, revealing remarkable mechanistic homologies in Ca²⁺-release function. Additionally, we discuss genomic analyses identifying this class of Ca²⁺ release channels in unicellular organisms and the implications of these data in understanding the molecular evolution of these fundamental receptors in nature.