2. Academic Validation
  3. Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites

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

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.

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