UC San Diego

Contacts between the endoplasmic reticulum (ER) and plasma membrane (PM) contain specialized tethering proteins that bind both ER and PM membranes. In excitable cells, ER-PM contacts play an important role in calcium signaling and transferring lipids. Junctophilins are a conserved family of ER-PM tethering proteins. They are predominantly expressed in muscles and neurons and known to simultaneously bind both ER- and PM-localized ion channels. Since their discovery two decades ago, functional studies using junctophilin-deficient animals have provided a deep understanding of their roles in muscles and neurons, including excitation-contraction coupling, store-operated calcium entry (SOCE), and afterhyperpolarization (AHP). In this review, we highlight key findings from mouse, fly, and worm that support evolutionary conservation of junctophilins.