Fiche publication
Date publication
août 2026
Journal
Science advances
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ALPY Fabien
,
Pr MELY Yves
,
Dr TOMASETTO Catherine
,
Dr RICHERT Ludovic
,
Mr HUMBERT Nicolas
,
Dr PRZYBILLA Frédéric
Tous les auteurs :
Takahashi K, Tomishige N, Abe M, Šolinc G, Rae J, Yamaji T, Przybilla F, Richert L, Humbert N, Uemura T, Wollert T, Waguri S, Hanada K, Sako Y, Anderluh G, Parton RG, Mély Y, Tomasetto C, Alpy F, Kobayashi T
Lien Pubmed
Résumé
The physiological role of lipid asymmetry in intracellular membranes remains poorly understood. Here, we show that sphingomyelin (SM), typically confined to the lumen of the trans-Golgi network (TGN), is exposed on its cytoplasmic surface by the action of the Golgi-associated protein, Golgi-associated gamma-adaptin ear-containing adenosine 5'-diphosphate-ribosylation factor-binding protein 1 (GGA1). This exposure is driven by the GGA1 GAT domain, which induces lipid scrambling in a manner dependent on membrane curvature and cholesterol. SM exposure coincides with the exit of mannose 6-phosphate receptors from the TGN, a process essential for lysosomal enzyme trafficking. Furthermore, SM is transferred to autophagic membranes, where it facilitates autophagosome-lysosome fusion. These findings reveal a previously unrecognized role for lipid remodeling in membrane trafficking and autophagy.
Mots clés
Autophagy, Lysosomes, metabolism, trans-Golgi Network, metabolism, Adaptor Proteins, Vesicular Transport, metabolism, Humans, Sphingomyelins, metabolism, Protein Transport, Receptor, IGF Type 2, metabolism, Animals, Autophagosomes, metabolism, Cholesterol, metabolism
Référence
Sci Adv. 2026 08 28;12(35):eaec4519
