RAL-1 controls multivesicular body biogenesis and exosome secretion

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 G...

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Bibliographic Details
Published in:The Journal of cell biology 2015-10, Vol.211 (1), p.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: Article
Language:English
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
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201504136