The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction.
The histone demethylase KDM5 is required for synaptic structure and function at the Drosophila neuromuscular junction.
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组蛋白去甲基化酶KDM5是果蝇神经肌肉接头突触结构和功能所必需的。
DOI：
10.1016/j.celrep.2021.108753
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发表时间：
2021-02-16
期刊：
影响因子：
8.8
通讯作者：
Secombe J
中科院分区：
文献类型：
--
作者：
Belalcazar HM;Hendricks EL;Zamurrad S;Liebl FLW;Secombe J
编码组蛋白脱甲基酶的赖氨酸脱甲基酶5（KDM5）家族的基因突变在智力残疾（ID）个体中观察到。尽管有明确的证据将KDM5功能与神经发育途径联系起来，但该蛋白质家族如何影响转录程序以介导突触结构和活性仍不清楚。使用果蝇幼虫的神经肌肉接头（NMJ），我们表明，KDM5需要突触前神经解剖的发展和突触功能。KDM5的Jumonji C（JmjC）结构域编码的组蛋白去甲基化酶活性，预计将被许多ID相关等位基因减少，是适当的突触形态和神经传递所必需的。C5HC2锌指的活性也是必需的，因为该基序中的ID相关突变减少了NMJ终扣数量，增加了终扣大小，并改变了微管动力学。因此，KDM5使用脱甲基酶依赖性和独立性机制来调节NMJ结构和活性，突出了这种染色质修饰剂执行其神经元基因调控程序的复杂性。组蛋白去甲基化酶的KDM5家族中的突变在智力残疾（ID）个体中观察到。Belalcazar等人表明，KDM5调节的转录在果蝇中对于适当的神经解剖学发育和神经传递是必需的。
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.
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影响因子：
64.5
作者：
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