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The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction
Mutations in the genes encoding the lysine demethylase 5 (KDM5) family of histone demethylases are observed in individuals with intellectual disability (ID). Despite clear evidence linking KDM5 function to neurodevelopmental pathways, how this family of proteins impacts transcriptional programs to m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945993/ https://www.ncbi.nlm.nih.gov/pubmed/33596422 http://dx.doi.org/10.1016/j.celrep.2021.108753 |
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author | Belalcazar, Helen M. Hendricks, Emily L. Zamurrad, Sumaira Liebl, Faith L.W. Secombe, Julie |
author_facet | Belalcazar, Helen M. Hendricks, Emily L. Zamurrad, Sumaira Liebl, Faith L.W. Secombe, Julie |
author_sort | Belalcazar, Helen M. |
collection | PubMed |
description | Mutations in the genes encoding the lysine demethylase 5 (KDM5) family of histone demethylases are observed in individuals with intellectual disability (ID). Despite clear evidence linking KDM5 function to neurodevelopmental pathways, how this family of proteins impacts transcriptional programs to mediate synaptic structure and activity remains unclear. Using the Drosophila larval neuromuscular junction (NMJ), we show that KDM5 is required presynaptically for neuroanatomical development and synaptic function. The Jumonji C (JmjC) domain-encoded histone demethylase activity of KDM5, which is expected to be diminished by many ID-associated alleles, is required for appropriate synaptic morphology and neurotransmission. The activity of the C5HC2 zinc finger is also required, as an ID-associated mutation in this motif reduces NMJ bouton number, increases bouton size, and alters microtubule dynamics. KDM5 therefore uses demethylase-dependent and independent mechanisms to regulate NMJ structure and activity, highlighting the complex nature by which this chromatin modifier carries out its neuronal gene-regulatory programs. |
format | Online Article Text |
id | pubmed-7945993 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-79459932021-03-10 The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction Belalcazar, Helen M. Hendricks, Emily L. Zamurrad, Sumaira Liebl, Faith L.W. Secombe, Julie Cell Rep Article Mutations in the genes encoding the lysine demethylase 5 (KDM5) family of histone demethylases are observed in individuals with intellectual disability (ID). Despite clear evidence linking KDM5 function to neurodevelopmental pathways, how this family of proteins impacts transcriptional programs to mediate synaptic structure and activity remains unclear. Using the Drosophila larval neuromuscular junction (NMJ), we show that KDM5 is required presynaptically for neuroanatomical development and synaptic function. The Jumonji C (JmjC) domain-encoded histone demethylase activity of KDM5, which is expected to be diminished by many ID-associated alleles, is required for appropriate synaptic morphology and neurotransmission. The activity of the C5HC2 zinc finger is also required, as an ID-associated mutation in this motif reduces NMJ bouton number, increases bouton size, and alters microtubule dynamics. KDM5 therefore uses demethylase-dependent and independent mechanisms to regulate NMJ structure and activity, highlighting the complex nature by which this chromatin modifier carries out its neuronal gene-regulatory programs. 2021-02-16 /pmc/articles/PMC7945993/ /pubmed/33596422 http://dx.doi.org/10.1016/j.celrep.2021.108753 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Belalcazar, Helen M. Hendricks, Emily L. Zamurrad, Sumaira Liebl, Faith L.W. Secombe, Julie The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction |
title | The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction |
title_full | The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction |
title_fullStr | The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction |
title_full_unstemmed | The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction |
title_short | The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction |
title_sort | histone demethylase kdm5 is required for synaptic structure and function at the drosophila neuromuscular junction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945993/ https://www.ncbi.nlm.nih.gov/pubmed/33596422 http://dx.doi.org/10.1016/j.celrep.2021.108753 |
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