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

被引：634

作者：

Hsu, Chieh ^{[1
]}

Morohashi, Yuichi ^{[5
]}

Yoshimura, Shin-ichiro ^{[5
]}

Manrique-Hoyos, Natalia ^{[1
]}

Jung, SangYong ^{[3
]}

Lauterbach, Marcel A. ^{[7
]}

Bakhti, Mostafa ^{[1
]}

Gronborg, Mads ^{[6
]}

Moebius, Wiebke ^{[2
]}

Rhee, JeongSeop ^{[3
]}

Barr, Francis A. ^{[5
]}

Simons, Mikael ^{[1
,4
]}

机构：

[1] Max Planck Inst Expt Med, D-37075 Gottingen, Germany

[2] Dept Neurogenet, D-37075 Gottingen, Germany

[3] Dept Mol Neurobiol, D-37075 Gottingen, Germany

[4] Univ Gottingen, Dept Neurol, D-37075 Gottingen, Germany

[5] Univ Liverpool, Canc Res Ctr, Liverpool L3 9TA, Merseyside, England

[6] Max Planck Inst Biophys Chem, Dept Neurobiol, D-37077 Gottingen, Germany

[7] Max Planck Inst Biophys Chem, Dept NanoBiophoton, D-37077 Gottingen, Germany

来源：

JOURNAL OF CELL BIOLOGY | 2010年 / 189卷 / 02期

基金：

英国惠康基金; 欧洲研究理事会;

关键词：

MULTIVESICULAR BODIES; MYELIN; CELL; IDENTIFICATION; VESICLES; BIOGENESIS; DISSECTION; MECHANISMS; COMPLEX; FUSION;

D O I：

10.1083/jcb.200911018

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：223 / 232

页数：10

共 46 条

[1] RETRACTED: Identification and characterization of microvesicles secreted by 3T3-L1 adipocytes: redox- and Hormone Dependent induction of milk fat globule-epidermal growth factor 8-associated microvesicles (Retracted article. See vol. 154, pg. 4437, 2013) [J].