ER–PM connections: sites of information transfer and inter-organelle communication

Abstract

Eukaryotic cells are divided into distinct membrane-bound organelles with unique identities and specialized metabolic functions. Communication between organelles must take place to regulate the size, shape, and composition of individual organelles, as well as to coordinate transport between organelles. The endoplasmic reticulum (ER) forms an expansive membrane network that contacts and participates in crosstalk with several other organelles in the cell, most notably the plasma membrane (PM). ER–PM junctions have well-established functions in the movement of small molecules, such as lipids and ions, between the ER and PM. Recent discoveries have revealed additional exciting roles for ER–PM junctions in the regulation of cell signaling, ER shape and architecture, and PM domain organization.

Activation of Ca2+‐activated Cl− channel ANO1 by localized Ca2+ signals

“…Such junctions are abundant in eukaryotic cells and are increasingly recognized as intracellular signalling ‘hubs’ (Stefan et al . 2013). We further hypothesized that plasmalemmal components of the signalling complex (i.e.…”

“…Thus, in yeast an anoctamin orthologue, Ist2, is apparently a tethering protein that holds plasma and ER membranes together to maintain plasma membrane–ER junctions (Stefan et al . 2013). In yeast, Ist2 localizes to the ER membrane extending its C‐terminus to the cytosol.…”

Three-dimensional architecture of extended synaptotagmin-mediated endoplasmic reticulum–plasma membrane contact sites

“…In SOCE, upon depletion of Ca 2+ in the ER, the ER protein stromal interaction molecule 1 (STIM1) oligomerizes, binds, and activates Orai1 Ca 2+ channels at the PM to drive influx of extracellular Ca 2+ , thereby allowing homeostatic regulation of ER Ca 2+ levels (3,4). However, growing evidence suggests that ER-PM contacts also play more general roles, including signaling (5,6) and the regulation of both lipid metabolism and transport between bilayers (1,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

“…E-Syt | cryo-electron microscopy | TULIP | phosphoinositides | lipid transfer T he endoplasmic reticulum (ER) consists of a complex network of tubules and cisternae that extends throughout the cell and forms close appositions ("contact sites") with other membranous organelles and with the plasma membrane (PM) (1,2). The best characterized function of ER-PM contacts is in Ca 2+ homeostasis, as ER-PM contacts mediate the excitationcontraction coupling in muscle and store-operated Ca 2+ entry (SOCE) in all metazoan cells.…”

TMEM110 regulates the maintenance and remodeling of mammalian ER–plasma membrane junctions competent for STIM–ORAI signaling

“…For example, the formation and maintenance of ER-plasma membrane junctions depends on tricalbins and other proteins in yeast cells (8)(9)(10) and in mammalian cells on the extended synaptotagmins (E-Syts), a family of three tricalbin homologs, and other unidentified proteins (11,12). The insights from yeast extend to the mechanisms of cellular lipid metabolism and lipid transfer between the apposed bilayers that have been conserved from yeast cells to human cells (13)(14)(15)(16)(17)(18)(19). On the other hand, parallels with yeast are less informative about processes specific to mammalian cells, including the storedependent calcium entry controlled by STIM-ORAI signaling.…”