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Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C
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 intracell...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856897/ https://www.ncbi.nlm.nih.gov/pubmed/20404108 http://dx.doi.org/10.1083/jcb.200911018 |
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author | Hsu, Chieh 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 |
author_facet | Hsu, Chieh 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 |
author_sort | Hsu, Chieh |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2856897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28568972010-10-19 Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C Hsu, Chieh 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 J Cell Biol Research Articles 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. The Rockefeller University Press 2010-04-19 /pmc/articles/PMC2856897/ /pubmed/20404108 http://dx.doi.org/10.1083/jcb.200911018 Text en © 2010 Hsu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Hsu, Chieh 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 Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C |
title | Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C |
title_full | Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C |
title_fullStr | Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C |
title_full_unstemmed | Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C |
title_short | Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A–C |
title_sort | regulation of exosome secretion by rab35 and its gtpase-activating proteins tbc1d10a–c |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856897/ https://www.ncbi.nlm.nih.gov/pubmed/20404108 http://dx.doi.org/10.1083/jcb.200911018 |
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