@article{d58a2fb27c1b45858e246e74e9d45f4c,
title = "The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction",
abstract = "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. 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.",
keywords = "Drosophila, KDM5, glutamatergic signaling, histone demethylase, intellectual disability, microtubule dynamics, motor neuron, neuromuscular junction, transcription",
author = "Belalcazar, {Helen M.} and Hendricks, {Emily L.} and Sumaira Zamurrad and Liebl, {Faith L.W.} and Julie Secombe",
note = "Funding Information: We thank members of the Secombe, Liebl, and Baker labs for their insights and comments on the manuscript. We also thank Jacqueline Tobin for her help as a summer student. We are grateful for the GluRIIC antibody from Dr. Aaron DiAntonio, fly strains from the Bloomington Drosophila Stock Center ( NIH P400D018537 ), and antibodies from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at the University of Iowa. We also thank the Analytical Imaging Facility and the Genomics Core at Einstein for their technical support. This work was supported by NIH funding to J.S. ( R01 GM112783 ) and F.L.W.L. ( 1R15NS101608-01A1 ), a shared instrument grant ( 1S10OD023591-01 ), and an Einstein Cancer Center support grant ( P30 CA013330 ). Funding Information: We thank members of the Secombe, Liebl, and Baker labs for their insights and comments on the manuscript. We also thank Jacqueline Tobin for her help as a summer student. We are grateful for the GluRIIC antibody from Dr. Aaron DiAntonio, fly strains from the Bloomington Drosophila Stock Center (NIH P400D018537), and antibodies from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at the University of Iowa. We also thank the Analytical Imaging Facility and the Genomics Core at Einstein for their technical support. This work was supported by NIH funding to J.S. (R01 GM112783) and F.L.W.L. (1R15NS101608-01A1), a shared instrument grant (1S10OD023591-01), and an Einstein Cancer Center support grant (P30 CA013330). Conceptualization, J.S. H.M.B. and F.L.W.L.; methodology, H.M.B.; investigation, H.M.B. S.Z. E.L.H. F.L.W.L. and J.S.; writing ? original draft, H.M.B. and J.S.; writing ? review & editing, H.M.B. J.S. F.L.W.L. and E.L.H.; funding acquisition, J.S. and F.L.W.L.; supervision, J.S. and F.L.W.L. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = feb,
day = "16",
doi = "10.1016/j.celrep.2021.108753",
language = "English (US)",
volume = "34",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",
}