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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555909/?tool=EBI |
| _version_ | 1818459832105041920 |
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| author | Diana Zala Maria-Victoria Hinckelmann Frédéric Saudou |
| author_facet | Diana Zala Maria-Victoria Hinckelmann Frédéric Saudou |
| author_sort | Diana Zala |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T23:20:37Z |
| format | Article |
| id | doaj.art-ab283d681b794817992153917fda8340 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T23:20:37Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ab283d681b794817992153917fda83402022-12-21T22:43:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e6016210.1371/journal.pone.0060162Huntingtin's function in axonal transport is conserved in Drosophila melanogaster.Diana ZalaMaria-Victoria HinckelmannFrédéric SaudouHuntington'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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555909/?tool=EBI |
| spellingShingle | Diana Zala Maria-Victoria Hinckelmann Frédéric Saudou Huntingtin's function in axonal transport is conserved in Drosophila melanogaster. PLoS ONE |
| title | 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_short | Huntingtin's function in axonal transport is conserved in Drosophila melanogaster. |
| title_sort | huntingtin s function in axonal transport is conserved in drosophila melanogaster |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23555909/?tool=EBI |
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