AUTHOR=Piggott Christopher A. , Jin Yishi 

TITLE=Junctophilins: Key Membrane Tethers in Muscles and Neurons

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 14 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2021.709390

DOI=10.3389/fnmol.2021.709390

ISSN=1662-5099

ABSTRACT=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, and afterhyperpolarization. In this review, we highlight key findings from mice, C. elegans, and D. melanogaster that support evolutionary conservation of junctophilins.