RRC ID 45577
Author Hyenne V, Apaydin A, Rodriguez D, Spiegelhalter C, Hoff-Yoessle S, Diem M, Tak S, Lefebvre O, Schwab Y, Goetz JG, Labouesse M.
Title RAL-1 controls multivesicular body biogenesis and exosome secretion.
Journal J Cell Biol
Abstract 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.
Volume 211(1)
Pages 27-37
Published 2015-10-12
DOI 10.1083/jcb.201504136
PII jcb.201504136
PMID 26459596
PMC PMC4602040
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / enzymology* Caenorhabditis elegans Proteins / physiology* Cell Membrane / enzymology Exosomes / metabolism* Membrane Fusion Multivesicular Bodies / metabolism* Protein Transport Qa-SNARE Proteins / metabolism ral GTP-Binding Proteins / physiology*
IF 8.811
Times Cited 62
WOS Category CELL BIOLOGY
Resource
C.elegans tm5205