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The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles
Endosomal sorting complex required for transport (ESCRT) complex proteins regulate biogenesis and release of extracellular vesicles (EVs), which enable cell-to-cell communication in the nervous system essential for development and adult function. We recently showed human loss-of-function (LOF) mutat...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178983/ https://www.ncbi.nlm.nih.gov/pubmed/30044992 http://dx.doi.org/10.1016/j.celrep.2018.06.100 |
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author | Coulter, Michael E. Dorobantu, Cristina M. Lodewijk, Gerrald A. Delalande, François Cianferani, Sarah Ganesh, Vijay S. Smith, Richard S. Lim, Elaine T. Xu, C. Shan Pang, Song Wong, Eric T. Lidov, Hart G.W. Calicchio, Monica L. Yang, Edward Gonzalez, Dilenny M. Schlaeger, Thorsten M. Mochida, Ganeshwaran H. Hess, Harald Allen Lee, Wei-Chung Lehtinen, Maria K. Kirchhausen, Tomas Haussler, David Jacobs, Frank M.J. Gaudin, Raphael Walsh, Christopher A. |
author_facet | Coulter, Michael E. Dorobantu, Cristina M. Lodewijk, Gerrald A. Delalande, François Cianferani, Sarah Ganesh, Vijay S. Smith, Richard S. Lim, Elaine T. Xu, C. Shan Pang, Song Wong, Eric T. Lidov, Hart G.W. Calicchio, Monica L. Yang, Edward Gonzalez, Dilenny M. Schlaeger, Thorsten M. Mochida, Ganeshwaran H. Hess, Harald Allen Lee, Wei-Chung Lehtinen, Maria K. Kirchhausen, Tomas Haussler, David Jacobs, Frank M.J. Gaudin, Raphael Walsh, Christopher A. |
author_sort | Coulter, Michael E. |
collection | PubMed |
description | Endosomal sorting complex required for transport (ESCRT) complex proteins regulate biogenesis and release of extracellular vesicles (EVs), which enable cell-to-cell communication in the nervous system essential for development and adult function. We recently showed human loss-of-function (LOF) mutations in ESCRT-III member CHMP1A cause autosomal recessive microcephaly with pontocerebellar hypoplasia, but its mechanism was unclear. Here, we show Chmp1a is required for progenitor proliferation in mouse cortex and cerebellum and progenitor maintenance in human cerebral organoids. In Chmp1a null mice, this defect is associated with impaired sonic hedgehog (Shh) secretion and intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs). Furthermore, we show CHMP1A is important for release of an EV subtype that contains AXL, RAB18, and TMED10 (ART) and SHH. Our findings show CHMP1A loss impairs secretion of SHH on ART-EVs, providing molecular mechanistic insights into the role of ESCRT proteins and EVs in the brain. |
format | Online Article Text |
id | pubmed-6178983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
record_format | MEDLINE/PubMed |
spelling | pubmed-61789832018-10-10 The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles Coulter, Michael E. Dorobantu, Cristina M. Lodewijk, Gerrald A. Delalande, François Cianferani, Sarah Ganesh, Vijay S. Smith, Richard S. Lim, Elaine T. Xu, C. Shan Pang, Song Wong, Eric T. Lidov, Hart G.W. Calicchio, Monica L. Yang, Edward Gonzalez, Dilenny M. Schlaeger, Thorsten M. Mochida, Ganeshwaran H. Hess, Harald Allen Lee, Wei-Chung Lehtinen, Maria K. Kirchhausen, Tomas Haussler, David Jacobs, Frank M.J. Gaudin, Raphael Walsh, Christopher A. Cell Rep Article Endosomal sorting complex required for transport (ESCRT) complex proteins regulate biogenesis and release of extracellular vesicles (EVs), which enable cell-to-cell communication in the nervous system essential for development and adult function. We recently showed human loss-of-function (LOF) mutations in ESCRT-III member CHMP1A cause autosomal recessive microcephaly with pontocerebellar hypoplasia, but its mechanism was unclear. Here, we show Chmp1a is required for progenitor proliferation in mouse cortex and cerebellum and progenitor maintenance in human cerebral organoids. In Chmp1a null mice, this defect is associated with impaired sonic hedgehog (Shh) secretion and intraluminal vesicle (ILV) formation in multivesicular bodies (MVBs). Furthermore, we show CHMP1A is important for release of an EV subtype that contains AXL, RAB18, and TMED10 (ART) and SHH. Our findings show CHMP1A loss impairs secretion of SHH on ART-EVs, providing molecular mechanistic insights into the role of ESCRT proteins and EVs in the brain. 2018-07-24 /pmc/articles/PMC6178983/ /pubmed/30044992 http://dx.doi.org/10.1016/j.celrep.2018.06.100 Text en This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Coulter, Michael E. Dorobantu, Cristina M. Lodewijk, Gerrald A. Delalande, François Cianferani, Sarah Ganesh, Vijay S. Smith, Richard S. Lim, Elaine T. Xu, C. Shan Pang, Song Wong, Eric T. Lidov, Hart G.W. Calicchio, Monica L. Yang, Edward Gonzalez, Dilenny M. Schlaeger, Thorsten M. Mochida, Ganeshwaran H. Hess, Harald Allen Lee, Wei-Chung Lehtinen, Maria K. Kirchhausen, Tomas Haussler, David Jacobs, Frank M.J. Gaudin, Raphael Walsh, Christopher A. The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles |
title | The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles |
title_full | The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles |
title_fullStr | The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles |
title_full_unstemmed | The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles |
title_short | The ESCRT-III Protein CHMP1A Mediates Secretion of Sonic Hedgehog on a Distinctive Subtype of Extracellular Vesicles |
title_sort | escrt-iii protein chmp1a mediates secretion of sonic hedgehog on a distinctive subtype of extracellular vesicles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178983/ https://www.ncbi.nlm.nih.gov/pubmed/30044992 http://dx.doi.org/10.1016/j.celrep.2018.06.100 |
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