ER-endosome Contact Sites: Molecular Compositions and Functions

EMBO J. 2015 Jul 14;34(14):1848-58. doi: 10.15252/embj.201591481. Epub 2015 Jun 3.


Recent studies have revealed the existence of numerous contact sites between the endoplasmic reticulum (ER) and endosomes in mammalian cells. Such contacts increase during endosome maturation and play key roles in cholesterol transfer, endosome positioning, receptor dephosphorylation, and endosome fission. At least 7 distinct contact sites between the ER and endosomes have been identified to date, which have diverse molecular compositions. Common to these contact sites is that they impose a close apposition between the ER and endosome membranes, which excludes membrane fusion while allowing the flow of molecular signals between the two membranes, in the form of enzymatic modifications, or ion, lipid, or protein transfer. Thus, ER-endosome contact sites ensure coordination of molecular activities between the two compartments while keeping their general compositions intact. Here, we review the molecular architectures and cellular functions of known ER-endosome contact sites and discuss their implications for human health.

Keywords: endoplasmic reticulum; endosome; membrane contact sites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Cytoskeleton / metabolism
  • Endoplasmic Reticulum / chemistry
  • Endoplasmic Reticulum / metabolism*
  • Endosomes / chemistry
  • Endosomes / metabolism*
  • Humans
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism


  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1