Endoplasmic Reticulum-Plasma Membrane Contact Sites

Annu Rev Biochem. 2017 Jun 20;86:659-684. doi: 10.1146/annurev-biochem-061516-044932. Epub 2017 Feb 23.


The endoplasmic reticulum (ER) has a broad localization throughout the cell and forms direct physical contacts with all other classes of membranous organelles, including the plasma membrane (PM). A number of protein tethers that mediate these contacts have been identified, and study of these protein tethers has revealed a multiplicity of roles in cell physiology, including regulation of intracellular Ca2+ dynamics and signaling as well as control of lipid traffic and homeostasis. In this review, we discuss the cross talk between the ER and the PM mediated by direct contacts. We review factors that tether the two membranes, their properties, and their dynamics in response to the functional state of the cell. We focus in particular on the role of ER-PM contacts in nonvesicular lipid transport between the two bilayers mediated by lipid transfer proteins.

Keywords: Ca2+ release-activated Ca2+ modulator; ORP; Orai; PITP; STIM; extended synaptotagmins; lipid transfer protein; oxysterol-binding protein (OSBP)–related protein; phosphatidylinositol transfer protein; stromal interaction molecule.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Calcium / metabolism*
  • Calcium Signaling
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • Eukaryotic Cells / metabolism
  • Eukaryotic Cells / ultrastructure
  • Gene Expression
  • Homeostasis
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • ORAI1 Protein / genetics
  • ORAI1 Protein / metabolism*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism
  • Stromal Interaction Molecule 1 / genetics
  • Stromal Interaction Molecule 1 / metabolism
  • Synaptotagmins / genetics
  • Synaptotagmins / metabolism


  • Carrier Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • ORAI1 Protein
  • Receptors, Steroid
  • STIM1 protein, human
  • Stromal Interaction Molecule 1
  • lipid transfer protein
  • oxysterol binding protein
  • Synaptotagmins
  • Calcium