RAL-1 controls multivesicular body biogenesis and exosome secretion.
Fiche publication
Date publication
octobre 2015
Journal
The Journal of cell biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GOETZ Jacky, Dr LEFEBVRE Olivier, Dr HYENNE Vincent
Tous les auteurs :
Hyenne V, Apaydin A, Rodriguez D, Spiegelhalter C, Hoff-Yoessle S, Diem M, Tak S, Lefebvre O, Schwab Y, Goetz JG, Labouesse M
Lien Pubmed
Résumé
Exosomes are secreted vesicles arising from the fusion of multivesicular bodies (MVBs) with the plasma membrane. Despite their importance in various processes, the molecular mechanisms controlling their formation and release remain unclear. Using nematodes and mammary tumor cells, we show that Ral GTPases are involved in exosome biogenesis. In Caenorhabditis elegans, RAL-1 localizes at the surface of secretory MVBs. A quantitative electron microscopy analysis of RAL-1-deficient animals revealed that RAL-1 is involved in both MVB formation and their fusion with the plasma membrane. These functions do not involve the exocyst complex, a common Ral guanosine triphosphatase (GTPase) effector. Furthermore, we show that the target membrane SNARE protein SYX-5 colocalizes with a constitutively active form of RAL-1 at the plasma membrane, and MVBs accumulate under the plasma membrane when SYX-5 is absent. In mammals, RalA and RalB are both required for the secretion of exosome-like vesicles in cultured cells. Therefore, Ral GTPases represent new regulators of MVB formation and exosome release.
Mots clés
Animals, Caenorhabditis elegans, cytology, Caenorhabditis elegans Proteins, physiology, Cell Membrane, enzymology, Exosomes, secretion, Membrane Fusion, Multivesicular Bodies, metabolism, Protein Transport, Qa-SNARE Proteins, metabolism, ral GTP-Binding Proteins, physiology
Référence
J. Cell Biol.. 2015 Oct;211(1):27-37