STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes and the ER

Fabien Alpy, Adrien Rousseau, Yannick Schwab, François Legueux, Isabelle Stoll, Corinne Wendling, Coralie Spiegelhalter, Pascal Kessler, Carole Mathelin, Marie-Christine Rio, Timothy P Levine, Catherine Tomasetto

Research output: Contribution to journalArticlepeer-review

121 Citations (Scopus)

Abstract

Inter-organelle membrane contacts sites (MCSs) are specific subcellular regions favoring the exchange of metabolites and information. We investigated the potential role of the late-endosomal membrane-anchored proteins StAR related lipid transfer domain-3 (STARD3) and STARD3 N-terminal like (STARD3NL) in the formation of MCSs involving late-endosomes (LEs). We demonstrate that both STARD3 and STARD3NL create MCSs between LEs and the endoplasmic reticulum (ER). STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. Together, they form an LE-ER tethering complex allowing heterologous membrane apposition. This LE-ER tethering complex affects organelle dynamics by altering the formation of endosomal tubules. An in situ proximity ligation assay between STARD3, STARD3NL and VAP proteins identified endogenous LE-ER MCS. Thus, we report here the identification of proteins involved in inter-organellar interaction.

Original languageEnglish
Pages (from-to)5500-12
Number of pages13
JournalJournal of Cell Science
Volume126
Issue numberPt 23
DOIs
Publication statusPublished - 29 Nov 2013

Keywords

  • Amino Acid Motifs
  • Animals
  • Biological Transport
  • Carrier Proteins/genetics
  • Endoplasmic Reticulum/metabolism
  • Endosomes/metabolism
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Intracellular Membranes/metabolism
  • Membrane Proteins/genetics
  • Molecular Sequence Data
  • Protein Isoforms/genetics
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Vesicular Transport Proteins/genetics

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