Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites

EMBO Rep. 2018 Jul;19(7):e45453. doi: 10.15252/embr.201745453. Epub 2018 Jun 1.


Membrane contact sites are cellular structures that mediate interorganelle exchange and communication. The two major tether proteins of the endoplasmic reticulum (ER), VAP-A and VAP-B, interact with proteins from other organelles that possess a small VAP-interacting motif, named FFAT [two phenylalanines (FF) in an acidic track (AT)]. In this study, using an unbiased proteomic approach, we identify a novel ER tether named motile sperm domain-containing protein 2 (MOSPD2). We show that MOSPD2 possesses a Major Sperm Protein (MSP) domain which binds FFAT motifs and consequently allows membrane tethering in vitro MOSPD2 is an ER-anchored protein, and it interacts with several FFAT-containing tether proteins from endosomes, mitochondria, or Golgi. Consequently, MOSPD2 and these organelle-bound proteins mediate the formation of contact sites between the ER and endosomes, mitochondria, or Golgi. Thus, we characterized here MOSPD2, a novel tethering component related to VAP proteins, bridging the ER with a variety of distinct organelles.

Keywords: ER–organelle contact; FFAT motif; VAP proteins; endoplasmic reticulum; membrane contact site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics
  • Animals
  • Binding Sites / genetics
  • Endoplasmic Reticulum / genetics*
  • Endoplasmic Reticulum / metabolism
  • Endosomes / genetics
  • Golgi Apparatus / genetics
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Mitochondrial Membranes / metabolism
  • Protein Binding
  • Proteomics
  • Receptors, Chemokine / genetics*
  • Spermatozoa / metabolism
  • Vesicular Transport Proteins / genetics*


  • MOSPD2 protein, human
  • Membrane Proteins
  • Receptors, Chemokine
  • VAPA protein, human
  • VAPB protein, human
  • Vesicular Transport Proteins