STARD3/STARD3NL and VAP make a novel molecular tether between late endosomes and the ER

Fabien Alpy (1) , Adrien Rousseau (1) , Yannick Schwab (1) , François Legueux (1) , Isabelle Stoll (1) , Corinne Wendling (1) , Coralie Spiegelhalter (1) , Pascal Kessler (1) , Carole Mathelin (2, 3) , Marie-Christine Rio (1) , Timothy P Levine (4) , Catherine Tomasetto (1)

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 UNISTRA - Université de Strasbourg
3 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
4 UCL - University College of London [London]

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 LEER tethering complex allowing heterologous membrane apposition. This LEER 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 LEER MCS. Thus, we report here the identification of proteins involved in inter-organellar interaction.

Mots clés: Endoplasmic reticulum; Endosome; Membrane contact site; MLN64; MENTHO; START domain; MENTAL domain

Domaines: Organisation et fonctions cellulaires [q-bio.SC]

Fabien Alpy, Adrien Rousseau, Yannick Schwab, François Legueux, Isabelle Stoll, et al.. STARD3/STARD3NL and VAP make a novel molecular tether between late endosomes and the ER. Journal of Cell Science, 2013, ⟨10.1242/jcs.139295⟩. ⟨hal-03409563⟩