Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.

Huntington's disease (HD) is a devastating dominantly inherited neurodegenerative disorder caused by an abnormal polyglutamine expansion in the N-terminal part of the huntingtin (HTT) protein. HTT is a large scaffold protein that interacts with more than a hundred proteins and is probably invol...

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Autores principales:	Diana Zala, Maria-Victoria Hinckelmann, Frédéric Saudou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ab283d681b794817992153917fda8340
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spelling	oai:doaj.org-article:ab283d681b794817992153917fda83402021-11-18T07:51:31ZHuntingtin's function in axonal transport is conserved in Drosophila melanogaster.1932-620310.1371/journal.pone.0060162https://doaj.org/article/ab283d681b794817992153917fda83402013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555909/?tool=EBIhttps://doaj.org/toc/1932-6203Huntington's disease (HD) is a devastating dominantly inherited neurodegenerative disorder caused by an abnormal polyglutamine expansion in the N-terminal part of the huntingtin (HTT) protein. HTT is a large scaffold protein that interacts with more than a hundred proteins and is probably involved in several cellular functions. The mutation is dominant, and is thought to confer new and toxic functions to the protein. However, there is emerging evidence that the mutation also alters HTT's normal functions. Therefore, HD models need to recapitulate this duality if they are to be relevant. Drosophila melanogaster is a useful in vivo model, widely used to study HD through the overexpression of full-length or N-terminal fragments of mutant human HTT. However, it is unclear whether Drosophila huntingtin (DmHTT) shares functions similar to the mammalian HTT. Here, we used various complementary approaches to analyze the function of DmHTT in fast axonal transport. We show that DmHTT interacts with the molecular motor dynein, associates with vesicles and co-sediments with microtubules. DmHTT co-localizes with Brain-derived neurotrophic factor (BDNF)-containing vesicles in rat cortical neurons and partially replaces mammalian HTT in a fast axonal transport assay. DmHTT-KO flies show a reduced fast axonal transport of synaptotagmin vesicles in motoneurons in vivo. These results suggest that the function of HTT in axonal transport is conserved between flies and mammals. Our study therefore validates Drosophila melanogaster as a model to study HTT function, and its dysfunction associated with HD.Diana ZalaMaria-Victoria HinckelmannFrédéric SaudouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e60162 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Diana Zala Maria-Victoria Hinckelmann Frédéric Saudou Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.
description	Huntington's disease (HD) is a devastating dominantly inherited neurodegenerative disorder caused by an abnormal polyglutamine expansion in the N-terminal part of the huntingtin (HTT) protein. HTT is a large scaffold protein that interacts with more than a hundred proteins and is probably involved in several cellular functions. The mutation is dominant, and is thought to confer new and toxic functions to the protein. However, there is emerging evidence that the mutation also alters HTT's normal functions. Therefore, HD models need to recapitulate this duality if they are to be relevant. Drosophila melanogaster is a useful in vivo model, widely used to study HD through the overexpression of full-length or N-terminal fragments of mutant human HTT. However, it is unclear whether Drosophila huntingtin (DmHTT) shares functions similar to the mammalian HTT. Here, we used various complementary approaches to analyze the function of DmHTT in fast axonal transport. We show that DmHTT interacts with the molecular motor dynein, associates with vesicles and co-sediments with microtubules. DmHTT co-localizes with Brain-derived neurotrophic factor (BDNF)-containing vesicles in rat cortical neurons and partially replaces mammalian HTT in a fast axonal transport assay. DmHTT-KO flies show a reduced fast axonal transport of synaptotagmin vesicles in motoneurons in vivo. These results suggest that the function of HTT in axonal transport is conserved between flies and mammals. Our study therefore validates Drosophila melanogaster as a model to study HTT function, and its dysfunction associated with HD.
format	article
author	Diana Zala Maria-Victoria Hinckelmann Frédéric Saudou
author_facet	Diana Zala Maria-Victoria Hinckelmann Frédéric Saudou
author_sort	Diana Zala
title	Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.
title_short	Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.
title_full	Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.
title_fullStr	Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.
title_full_unstemmed	Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.
title_sort	huntingtin's function in axonal transport is conserved in drosophila melanogaster.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/ab283d681b794817992153917fda8340
work_keys_str_mv	AT dianazala huntingtinsfunctioninaxonaltransportisconservedindrosophilamelanogaster AT mariavictoriahinckelmann huntingtinsfunctioninaxonaltransportisconservedindrosophilamelanogaster AT fredericsaudou huntingtinsfunctioninaxonaltransportisconservedindrosophilamelanogaster
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Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.

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