Endoplasmic Reticulum-Plasma Membrane Junctions as Sites of Depolarization-Induced Ca2+ Signaling in Excitable Cells

Annu Rev Physiol. 2023 Feb 10:85:217-243. doi: 10.1146/annurev-physiol-032122-104610. Epub 2022 Oct 6.

Abstract

Membrane contact sites between endoplasmic reticulum (ER) and plasma membrane (PM), or ER-PM junctions, are found in all eukaryotic cells. In excitable cells they play unique roles in organizing diverse forms of Ca2+ signaling as triggered by membrane depolarization. ER-PM junctions underlie crucial physiological processes such as excitation-contraction coupling, smooth muscle contraction and relaxation, and various forms of activity-dependent signaling and plasticity in neurons. In many cases the structure and molecular composition of ER-PM junctions in excitable cells comprise important regulatory feedback loops linking depolarization-induced Ca2+ signaling at these sites to the regulation of membrane potential. Here, we describe recent findings on physiological roles and molecular composition of native ER-PM junctions in excitable cells. We focus on recent studies that provide new insights into canonical forms of depolarization-induced Ca2+ signaling occurring at junctional triads and dyads of striated muscle, as well as the diversity of ER-PM junctions in these cells and in smooth muscle and neurons.

Keywords: cardiac muscle; ion channel; membrane contact sites; neuron; second messenger; skeletal muscle; smooth muscle.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Calcium / metabolism
  • Calcium Signaling / physiology
  • Cell Membrane / metabolism
  • Endoplasmic Reticulum* / metabolism
  • Humans
  • Membrane Proteins* / physiology
  • Neurons / metabolism
  • Signal Transduction

Substances

  • Membrane Proteins
  • Calcium