TY - JOUR
T1 - Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C
AU - Hsu, Chieh
AU - Morohashi, Yuichi
AU - Yoshimura, Shin Ichiro
AU - Manrique-Hoyos, Natalia
AU - Jung, Sang Yong
AU - Lauterbach, Marcel A.
AU - Bakhti, Mostafa
AU - Grønborg, Mads
AU - Möbius, Wiebke
AU - Rhee, Jeong Seop
AU - Barr, Francis A.
AU - Simons, Mikael
PY - 2010/4/19
Y1 - 2010/4/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77951183654&partnerID=8YFLogxK
U2 - 10.1083/jcb.200911018
DO - 10.1083/jcb.200911018
M3 - Article
C2 - 20404108
AN - SCOPUS:77951183654
SN - 0021-9525
VL - 189
SP - 223
EP - 232
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 2
ER -