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The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development
The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, monogenic neurodegenerative disorders with an early onset in infancy or childhood. Despite identification of the genes disrupted in each form of the disease, their normal cellular role and how their deficits lead to disease pathology is...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821864/ https://www.ncbi.nlm.nih.gov/pubmed/31666534 http://dx.doi.org/10.1038/s41598-019-51588-w |
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author | Connolly, Kyle J. O’Hare, Megan B. Mohammed, Alamin Aitchison, Katelyn M. Anthoney, Niki C. Taylor, Matthew J. Stewart, Bryan A. Tuxworth, Richard I. Tear, Guy |
author_facet | Connolly, Kyle J. O’Hare, Megan B. Mohammed, Alamin Aitchison, Katelyn M. Anthoney, Niki C. Taylor, Matthew J. Stewart, Bryan A. Tuxworth, Richard I. Tear, Guy |
author_sort | Connolly, Kyle J. |
collection | PubMed |
description | The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, monogenic neurodegenerative disorders with an early onset in infancy or childhood. Despite identification of the genes disrupted in each form of the disease, their normal cellular role and how their deficits lead to disease pathology is not fully understood. Cln7, a major facilitator superfamily domain-containing protein, is affected in a late infantile-onset form of NCL. Cln7 is conserved across species suggesting a common function. Here we demonstrate that Cln7 is required for the normal growth of synapses at the Drosophila larval neuromuscular junction. In a Cln7 mutant, synapses fail to develop fully leading to reduced function and behavioral changes with dysregulation of TOR activity. Cln7 expression is restricted to the post-synaptic cell and the protein localizes to vesicles immediately adjacent to the post-synaptic membrane. Our data suggest an involvement for Cln7 in regulating trans-synaptic communication necessary for normal synapse development. |
format | Online Article Text |
id | pubmed-6821864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68218642019-11-05 The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development Connolly, Kyle J. O’Hare, Megan B. Mohammed, Alamin Aitchison, Katelyn M. Anthoney, Niki C. Taylor, Matthew J. Stewart, Bryan A. Tuxworth, Richard I. Tear, Guy Sci Rep Article The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, monogenic neurodegenerative disorders with an early onset in infancy or childhood. Despite identification of the genes disrupted in each form of the disease, their normal cellular role and how their deficits lead to disease pathology is not fully understood. Cln7, a major facilitator superfamily domain-containing protein, is affected in a late infantile-onset form of NCL. Cln7 is conserved across species suggesting a common function. Here we demonstrate that Cln7 is required for the normal growth of synapses at the Drosophila larval neuromuscular junction. In a Cln7 mutant, synapses fail to develop fully leading to reduced function and behavioral changes with dysregulation of TOR activity. Cln7 expression is restricted to the post-synaptic cell and the protein localizes to vesicles immediately adjacent to the post-synaptic membrane. Our data suggest an involvement for Cln7 in regulating trans-synaptic communication necessary for normal synapse development. Nature Publishing Group UK 2019-10-30 /pmc/articles/PMC6821864/ /pubmed/31666534 http://dx.doi.org/10.1038/s41598-019-51588-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Connolly, Kyle J. O’Hare, Megan B. Mohammed, Alamin Aitchison, Katelyn M. Anthoney, Niki C. Taylor, Matthew J. Stewart, Bryan A. Tuxworth, Richard I. Tear, Guy The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development |
title | The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development |
title_full | The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development |
title_fullStr | The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development |
title_full_unstemmed | The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development |
title_short | The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development |
title_sort | neuronal ceroid lipofuscinosis protein cln7 functions in the postsynaptic cell to regulate synapse development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821864/ https://www.ncbi.nlm.nih.gov/pubmed/31666534 http://dx.doi.org/10.1038/s41598-019-51588-w |
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