RAL-1 controls multivesicular body biogenesis and exosome secretion

• Published in: The Journal of cell biology Vol. 211; no. 1; pp. 27 - 37
• Main Authors: Hyenne, Vincent, Apaydin, Ahmet, Rodriguez, David, Spiegelhalter, Coralie, Hoff-Yoessle, Sarah, Diem, Maxime, Tak, Saurabh, Lefebvre, Olivier, Schwab, Yannick, Goetz, Jacky G, Labouesse, Michel
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 12-10-2015; The Rockefeller University Press
• Subjects: Animals; Biosynthesis; Caenorhabditis elegans - cytology; Caenorhabditis elegans - enzymology; Caenorhabditis elegans Proteins - physiology; Cell culture; Cell Membrane - enzymology; Development Biology; Enzymes; Exosomes - secretion; Life Sciences; Membrane Fusion; Membranes; Microscopy; Multivesicular Bodies - metabolism; Nematodes; Protein Transport; Qa-SNARE Proteins - metabolism; ral GTP-Binding Proteins - physiology; Tumors
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201504136

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.