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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2dfeb1df3f464c07b371924c3830b445
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spelling	oai:doaj.org-article:2dfeb1df3f464c07b371924c3830b4452021-12-02T15:07:53ZThe neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development10.1038/s41598-019-51588-w2045-2322https://doaj.org/article/2dfeb1df3f464c07b371924c3830b4452019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51588-whttps://doaj.org/toc/2045-2322Abstract 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.Kyle J. ConnollyMegan B. O’HareAlamin MohammedKatelyn M. AitchisonNiki C. AnthoneyMatthew J. TaylorBryan A. StewartRichard I. TuxworthGuy TearNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	neuronal ceroid lipofuscinosis protein cln7 functions in the postsynaptic cell to regulate synapse development
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/2dfeb1df3f464c07b371924c3830b445
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The neuronal ceroid lipofuscinosis protein Cln7 functions in the postsynaptic cell to regulate synapse development

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