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

• Published in: EMBO reports Vol. 19; no. 7
• Main Authors: Di Mattia, Thomas, Wilhelm, Léa P, Ikhlef, Souade, Wendling, Corinne, Spehner, Danièle, Nominé, Yves, Giordano, Francesca, Mathelin, Carole, Drin, Guillaume, Tomasetto, Catherine, Alpy, Fabien
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2018; Blackwell Publishing Ltd; EMBO Press; John Wiley and Sons Inc
• Subjects: Amino Acid Motifs - genetics; Animals; Binding Sites - genetics; Cellular structure; EMBO20; Endoplasmic reticulum; Endoplasmic Reticulum - genetics; Endoplasmic Reticulum - metabolism; Endosomes; Endosomes - genetics; ER–organelle contact; FFAT motif; Golgi apparatus; Golgi Apparatus - genetics; Homology; Humans; Life Sciences; Male; membrane contact site; Membrane proteins; Membrane Proteins - genetics; Membranes; Mice; Mitochondria; Mitochondrial Membranes - metabolism; Organelles; Protein Binding; Proteins; Proteomics; Receptors, Chemokine - genetics; Sperm; Spermatozoa - metabolism; Tethering; VAP proteins; Vesicular Transport Proteins - genetics; FFAT motif; membrane contact site; VAP proteins; ER–organelle contact; endoplasmic reticulum
• ISSN: 1469-221X; 1469-3178; 1469-3178
• DOI: 10.15252/embr.201745453

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. Synopsis The endoplasmic reticulum (ER) makes physical contacts with most cellular organelles. MOSPD2 (motile sperm domain‐containing protein 2) is a new ER‐anchored receptor, which binds FFAT (two phenylalanines in an acidic track)‐motif containing proteins. Analogous to vesicle‐associated membrane protein‐associated protein (VAP)‐A and VAP‐B, MOSPD2 mediates the formation of contact sites between the ER and a variety of organelles (including endosomes, mitochondria or Golgi). Motile sperm domain‐containing protein 2 (MOSPD2) is a novel ER‐anchored VAP homolog. The FFAT motif is recognized by the Major Sperm Protein (MSP) domain of MOSPD2. MOSPD2 interacts with a variety of organelle (endosomes, mitochondria or Golgi)‐bound proteins and thereby builds membrane contact sites. Graphical Abstract The endoplasmic reticulum (ER) makes physical contacts with most cellular organelles. This study identifies MOSPD2 as a new ER‐anchored receptor, which binds FFAT‐motif containing proteins in other organelles such as Golgi, endosomes and mitochondria.