The Endoplasmic Reticulum-Plasma Membrane Junction: A Hub for Agonist Regulation of Ca Entry.

Stimulation of cell-surface receptors induces cytosolic Ca ([Ca]) increases that are detected and transduced by effector proteins for regulation of cell function. Intracellular Ca release, via endoplasmic reticulum (ER) proteins inositol 1,4,5-trisphosphate receptors (IPR) and ryanodine receptors (RyR), and Ca influx, via store-operated Ca entry (SOCE), contribute to the increase in [Ca] The amplitude, frequency, and spatial characteristics of the [Ca] 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 (PIP), and culminates with the activation of IPR in the ER. Conversely, SOCE is initiated in the ER by Ca-sensing stromal interaction molecule (STIM) proteins, which then interact with PM channels Orai1 and TRPC1 to activate Ca entry. This review will address how ER-PM junctions serve a central role in agonist regulation of SOCE.

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