The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction
| Autor: | Helen M. Belalcazar, Sumaira Zamurrad, Emily L. Hendricks, Julie Secombe, Faith L.W. Liebl |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Neuromuscular Junction Neurotransmission medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Neuromuscular junction 03 medical and health sciences 0302 clinical medicine medicine Animals Drosophila Proteins Histone demethylase activity Histone Demethylases Zinc finger Mutation biology fungi Cell biology 030104 developmental biology medicine.anatomical_structure Histone nervous system biology.protein Demethylase Drosophila Female 030217 neurology & neurosurgery |
| Zdroj: | Cell reports |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2021.108753 |
| Popis: | SUMMARY 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. Graphical Abstract In Brief Mutations in the KDM5 family of histone demethylases are observed in individuals with intellectual disability (ID). Belalcazar et al. show that KDM5-regulated transcription is necessary in Drosophila for proper neuroanatomical development and neurotransmission at the glutamatergic larval neuromuscular junction. |
| Databáze: | OpenAIRE |
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