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额颞叶痴呆致病基因chmp2b对果蝇昼夜节律的作用和调控机制
首发时间：2024-07-26
摘要：一些额颞叶痴呆患者会伴有昼夜节律紊乱的症状，为探究额颞叶痴呆致病基因chmp2b对昼夜节律的作用及调控机制，我们以果蝇为模型，通过对时钟神经元过表达人源突变体chmp2bintron5和色素驱散因子（pigment dispersing factor, pdf）阳性神经元中干扰chmp2b的果蝇生物节律和行为进行检测，发现chmp2b主要在pdf阳性神经元中发挥对果蝇生物节律的调控作用；且过表达chmp2bintron5会导致slnv中period(per)蛋白的减少，遗传学实验证实同时过表达per能够挽救chmp2bintron5导致的果蝇生物节律紊乱；在果蝇s2细胞中探究per减少的分子机制，结果表明chmp2bintron5是通过增加per蛋白的泛素化降解，从而导致果蝇昼夜节律紊乱。
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the role and regulatory mechanism of frontotemporal dementia related gene chmp2b in drosophila circadian rhythm
abstract：some patients with frontotemporal dementia are accompanied by symptoms of circadian rhythm disturbance. in order to explore the role and regulatory mechanism of frontotemporal dementia gene chmp2b on circadian rhythm, we used drosophila melanogaster as a model. by detecting the circadian rhythms and behavior of drosophila melanogaster that overexpress the human mutant chmp2bintron5 in pigment dispersing factor (pdf) positive neurons and interfere with chmp2b in clock neurons , it was found that chmp2b mainly plays a regulatory role in the circadian rhythm of drosophila melanogaster in pdf-positive neurons. in addition, overexpression of chmp2bintron5 can lead to the decrease of period(per) protein in slnv, and genetic experiments have confirmed that simultaneous overexpression of per can save the biological rhythm disorder caused by chmp2bintron5 in drosophila. the molecular mechanism of per reduction was explored in s2 cells of drosophila melanogaster. the results showed that chmp2bintron5 caused circadian rhythm disturbance by increasing ubiquitination degradation of per protein
keywords： cell biology biological rhythm frontotemporal dementia chmp2b
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额颞叶痴呆致病基因chmp2b对果蝇昼夜节律的作用和调控机制
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