The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development
Abstract 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 pat...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2019-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-019-51588-w |
| _version_ | 1818991404785860608 |
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| author | Kyle J. Connolly Megan B. O’Hare Alamin Mohammed Katelyn M. Aitchison Niki C. Anthoney Matthew J. Taylor Bryan A. Stewart Richard I. Tuxworth Guy Tear |
| author_facet | Kyle J. Connolly Megan B. O’Hare Alamin Mohammed Katelyn M. Aitchison Niki C. Anthoney Matthew J. Taylor Bryan A. Stewart Richard I. Tuxworth Guy Tear |
| author_sort | Kyle J. Connolly |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T20:09:44Z |
| format | Article |
| id | doaj.art-2dfeb1df3f464c07b371924c3830b445 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T20:09:44Z |
| publishDate | 2019-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2dfeb1df3f464c07b371924c3830b4452022-12-21T19:27:50ZengNature PortfolioScientific Reports2045-23222019-10-019111410.1038/s41598-019-51588-wThe neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse developmentKyle J. Connolly0Megan B. O’Hare1Alamin Mohammed2Katelyn M. Aitchison3Niki C. Anthoney4Matthew J. Taylor5Bryan A. Stewart6Richard I. Tuxworth7Guy Tear8Institute of Cancer and Genomic Sciences, University of BirminghamDepartment of Developmental Neurobiology, King’s College London, New Hunt’s HouseInstitute of Cancer and Genomic Sciences, University of BirminghamInstitute of Cancer and Genomic Sciences, University of BirminghamInstitute of Cancer and Genomic Sciences, University of BirminghamInstitute of Cancer and Genomic Sciences, University of BirminghamDepartment of Biology, University of Toronto MississaugaInstitute of Cancer and Genomic Sciences, University of BirminghamDepartment of Developmental Neurobiology, King’s College London, New Hunt’s HouseAbstract 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.https://doi.org/10.1038/s41598-019-51588-w |
| spellingShingle | Kyle J. Connolly Megan B. O’Hare Alamin Mohammed Katelyn M. Aitchison Niki C. Anthoney Matthew J. Taylor Bryan A. Stewart Richard I. Tuxworth Guy Tear The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-019-51588-w |
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