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

  • EMBO Rep. 2018 Jul;19(7):e45453. doi: 10.15252/embr.201745453.
Thomas Di Mattia  1  2  3  4 ,  Léa P Wilhelm  1  2  3  4 ,  Souade Ikhlef  5 ,  Corinne Wendling  1  2  3  4 ,  Danièle Spehner  1  2  3  4 ,  Yves Nominé  1  2  3  4 ,  Francesca Giordano  6 ,  Carole Mathelin  1  2  3  4  7 ,  Guillaume Drin  5 ,  Catherine Tomasetto  8  2  3  4 ,  Fabien Alpy  8  2  3  4
Affiliations
  • 1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.
  • 2. Institut National de la Santé et de la Recherche Médicale (INSERM), U1258, Illkirch, France.
  • 3. Centre National de la Recherche Scientifique (CNRS), UMR7104, Illkirch, France.
  • 4. Université de Strasbourg, Illkirch, France.
  • 5. CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, Valbonne, France.
  • 6. Institut de Biologie Intégrative de la Cellule, CEA, CNRS, Paris-Sud University Paris-Saclay University, Gif-sur-Yvette Cedex 91198, France.
  • 7. Senology Unit, Strasbourg University Hospital (CHRU), Hôpital de Hautepierre, Strasbourg, France.
  • 8. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France [email protected] [email protected].
PMID: 29858488 DOI: 10.15252/embr.201745453
Abstract

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.