Cargando…
The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum
The Moonwalker (Mwk) mouse is a model of dominantly inherited cerebellar ataxia caused by a gain-of-function mutation in the transient receptor potential (TRP) channel TRPC3. Here, we report impairments in dendritic growth and synapse formation early on during Purkinje cell development in the Mwk ce...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476454/ https://www.ncbi.nlm.nih.gov/pubmed/25908616 http://dx.doi.org/10.1093/hmg/ddv150 |
_version_ | 1782377602770534400 |
---|---|
author | Dulneva, Anna Lee, Sheena Oliver, Peter L. Di Gleria, Katalin Kessler, Benedikt M. Davies, Kay E. Becker, Esther B. E. |
author_facet | Dulneva, Anna Lee, Sheena Oliver, Peter L. Di Gleria, Katalin Kessler, Benedikt M. Davies, Kay E. Becker, Esther B. E. |
author_sort | Dulneva, Anna |
collection | PubMed |
description | The Moonwalker (Mwk) mouse is a model of dominantly inherited cerebellar ataxia caused by a gain-of-function mutation in the transient receptor potential (TRP) channel TRPC3. Here, we report impairments in dendritic growth and synapse formation early on during Purkinje cell development in the Mwk cerebellum that are accompanied by alterations in calcium signaling. To elucidate the molecular effector pathways that regulate Purkinje cell dendritic arborization downstream of mutant TRPC3, we employed transcriptomic analysis of developing Purkinje cells isolated by laser-capture microdissection. We identified significant gene and protein expression changes in molecules involved in lipid metabolism. Consistently, lipid homeostasis in the Mwk cerebellum was found to be disturbed, and treatment of organotypic cerebellar slices with ceramide significantly improved dendritic outgrowth of Mwk Purkinje cells. These findings provide the first mechanistic insights into the TRPC3-dependent mechanisms, by which activated calcium signaling is coupled to lipid metabolism and the regulation of Purkinje cell development in the Mwk cerebellum. |
format | Online Article Text |
id | pubmed-4476454 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44764542015-06-24 The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum Dulneva, Anna Lee, Sheena Oliver, Peter L. Di Gleria, Katalin Kessler, Benedikt M. Davies, Kay E. Becker, Esther B. E. Hum Mol Genet Articles The Moonwalker (Mwk) mouse is a model of dominantly inherited cerebellar ataxia caused by a gain-of-function mutation in the transient receptor potential (TRP) channel TRPC3. Here, we report impairments in dendritic growth and synapse formation early on during Purkinje cell development in the Mwk cerebellum that are accompanied by alterations in calcium signaling. To elucidate the molecular effector pathways that regulate Purkinje cell dendritic arborization downstream of mutant TRPC3, we employed transcriptomic analysis of developing Purkinje cells isolated by laser-capture microdissection. We identified significant gene and protein expression changes in molecules involved in lipid metabolism. Consistently, lipid homeostasis in the Mwk cerebellum was found to be disturbed, and treatment of organotypic cerebellar slices with ceramide significantly improved dendritic outgrowth of Mwk Purkinje cells. These findings provide the first mechanistic insights into the TRPC3-dependent mechanisms, by which activated calcium signaling is coupled to lipid metabolism and the regulation of Purkinje cell development in the Mwk cerebellum. Oxford University Press 2015-07-15 2015-04-23 /pmc/articles/PMC4476454/ /pubmed/25908616 http://dx.doi.org/10.1093/hmg/ddv150 Text en © The Author 2015. Published by Oxford University Press http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Dulneva, Anna Lee, Sheena Oliver, Peter L. Di Gleria, Katalin Kessler, Benedikt M. Davies, Kay E. Becker, Esther B. E. The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum |
title | The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum |
title_full | The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum |
title_fullStr | The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum |
title_full_unstemmed | The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum |
title_short | The mutant Moonwalker TRPC3 channel links calcium signaling to lipid metabolism in the developing cerebellum |
title_sort | mutant moonwalker trpc3 channel links calcium signaling to lipid metabolism in the developing cerebellum |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476454/ https://www.ncbi.nlm.nih.gov/pubmed/25908616 http://dx.doi.org/10.1093/hmg/ddv150 |
work_keys_str_mv | AT dulnevaanna themutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT leesheena themutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT oliverpeterl themutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT digleriakatalin themutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT kesslerbenediktm themutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT davieskaye themutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT beckerestherbe themutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT dulnevaanna mutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT leesheena mutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT oliverpeterl mutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT digleriakatalin mutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT kesslerbenediktm mutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT davieskaye mutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum AT beckerestherbe mutantmoonwalkertrpc3channellinkscalciumsignalingtolipidmetabolisminthedevelopingcerebellum |