ER-PM junctions are subcellular sites where the endoplasmic reticulum (ER) and the plasma membrane (PM) are kept in close appositions, providing a platform for inter-organelle contact. These membrane contact sites are important for many physiological functions in mammalian cells, including excitation-contraction coupling, store-operated Ca2+ entry, and non-vesicular transfer of lipids between the ER and the PM. Here we review recent insights into the 3D structure and spatial organization of ER-PM junctions in mammalian cells as well as molecular mechanisms underlying the formation and functions of mammalian ER-PM junctions.
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