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PMID: 20404108 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C.

The Journal of cell biology ·Vol. 189 ·No. 2 ·2010-04-19 ·Pages 223-32

Hsu C, Morohashi Y, Yoshimura S, Manrique-Hoyos N, Jung S, Lauterbach MA, Bakhti M, Grønborg M, Möbius W, Rhee J, Barr FA, Simons M

Abstract

Oligodendrocytes secrete vesicles into the extracellular space, where they might play a role in neuron-glia communication. These exosomes are small vesicles with a diameter of 50-100 nm that are formed within multivesicular bodies and are released after fusion with the plasma membrane. The intracellular pathways that generate exosomes are poorly defined. Because Rab family guanosine triphosphatases (GTPases) together with their regulators are important membrane trafficking organizers, we investigated which Rab GTPase-activating proteins interfere with exosome release. We find that TBC1D10A-C regulate exosome secretion in a catalytic activity-dependent manner. We show that Rab35 is the target of TBC1D10A-C and that the inhibition of Rab35 function leads to intracellular accumulation of endosomal vesicles and impairs exosome secretion. Rab35 localizes to the surface of oligodendroglia in a GTP-dependent manner, where it increases the density of vesicles, suggesting a function in docking or tethering. These findings provide a basis for understanding the biogenesis and function of exosomes in the central nervous system.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Animals Calcium/metabolism Cell Line Cell Membrane/metabolism Exocytosis/physiology Exosomes/metabolism GTPase-Activating Proteins/genetics,metabolism Humans Mice Oligodendroglia/cytology,physiology Patch-Clamp Techniques RNA, Small Interfering/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism rab GTP-Binding Proteins/genetics,metabolism
Chemicals
Adaptor Proteins, Signal Transducing GTPase-Activating Proteins RNA, Small Interfering Recombinant Fusion Proteins TBC1D10A protein, human TBC1D10C protein, human RAB35 protein, human rab GTP-Binding Proteins Calcium
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Hsu Chieh
Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
Morohashi Yuichi
Yoshimura Shin-Ichiro
Manrique-Hoyos Natalia
Jung Sangyong
Lauterbach Marcel A
Bakhti Mostafa
Grønborg Mads
Möbius Wiebke
Rhee Jeongseop
Barr Francis A
Simons Mikael
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200911018
Published
2010-04-19
Pages
223-32
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2856897
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1083/jcb.200911018 PMC Full Text View journal details
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