The Endoplasmic Reticulum–Plasma Membrane Junction: A Hub for Agonist Regulation of Ca2+ Entry

• Published in: Cold Spring Harbor perspectives in biology Vol. 12; no. 2
• Main Authors: Ong, Hwei Ling, Ambudkar, Indu Suresh
• Format: Journal Article
• Language: English
• Published: Woodbury Cold Spring Harbor Laboratory Press 01.02.2020
• Subjects: Agonists; Calcium (intracellular); Calcium (reticular); Calcium channels; Calcium influx; Calcium ions; Cell surface; Endoplasmic reticulum; Frequency dependence; Inositol 1,4,5-trisphosphate receptors; Lipids; Membranes; Orai1 protein; PERSPECTIVES; Phosphatidylinositol 4,5-diphosphate; Phospholipase; Phospholipase C; Proteins; Receptors; Ryanodine receptors; Signaling
• ISSN: 1943-0264
• DOI: 10.1101/cshperspect.a035253

Stimulation of cell-surface receptors induces cytosolic Ca2+ ([Ca2+]i) increases that are detected and transduced by effector proteins for regulation of cell function. Intracellular Ca2+ release, via endoplasmic reticulum (ER) proteins inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR), and Ca2+ influx, via store-operated Ca2+ entry (SOCE), contribute to the increase in [Ca2+]i. The amplitude, frequency, and spatial characteristics of the [Ca2+]i increases are controlled by the compartmentalization of proteins into signaling complexes such as receptor-signaling complexes and SOCE complexes. Both complexes include protein and lipid components, located in the plasma membrane (PM) and ER. Receptor signaling initiates in the PM via phospholipase C (PLC)-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), and culminates with the activation of IP3R in the ER. Conversely, SOCE is initiated in the ER by Ca2+-sensing stromal interaction molecule (STIM) proteins, which then interact with PM channels Orai1 and TRPC1 to activate Ca2+ entry. This review will address how ER–PM junctions serve a central role in agonist regulation of SOCE.