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Updated: Jun 12, 2025

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DEPDC5通过与基特异性蛋白酶46相互作用来调节激发性突触传递的强度

Maria Sabina Cerullo¹, Caterina Canevari², Antonella Marte³

¹Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Largo Rosanna Benzi 10, 16132 Genova, Italy; IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genova, Italy.

Neurobiology of disease

|June 4, 2025

概括

DEPDC5突变通过增加激发性突触强度导致焦点. 这通过mTORC1过活性发生,导致更高的GluA1 AMPA受体密度和受损的谷氨酸信号传递.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
遗传学遗传学是一个

背景情况:

在DEPDC5中失去功能突变是与mTOR过度激活相关的焦点的最常见原因.
DEPDC5突变破坏了GATOR1复合体,抑制了mTORC1的信号传递.
之前的研究表明,DEPDC5损失导致神经元激发/抑制失衡,激发突触强度增加.

研究的目的:

研究将DEPDC5损失,mTORC1过活和激发性突触传输增加联系在一起的分子机制.
确定DEPDC5相互作用蛋白及其在调节谷氨酸受体功能的作用.

主要方法:

在成熟神经元中Depdc5缺失的条件淘汰 (cKO) 鼠标模型.
电生理学记录以评估激发性和抑制性突触传输.
生物化学试验分析蛋白质相互作用,无处不在和受体贩运.

主要成果:

Depdc5 cKO神经元表现出激发性传递和谷氨酸定量大小的增加,与正常的抑制性传递.
在Depdc5 cKO神经元中的血膜上增加了含有GluA1的AMPA受体密度.
DEPDC5与USP46相互作用,这是一种调节GluA1的二维基因酶;Depdc5的损失增加了USP46的水平,并降低了GluA1的无处不在.
过度表达USP46和增加的谷氨酸定量大小是通过USP46敲击或拉巴胺治疗来挽救的,这表明mTORC1依赖.

结论:

DEPDC5/mTORC1通路负面调节USP46活性和AMPA受体二维基因化,控制激发性突触强度.
这种途径的失调有助于DEPDC5相关,通过增加刺激性传播.

关键词:

在AMPA受体中,AMPA受体具有在DEPDC5交互原子中,DEPDC5是DEPDC5的交互原子.根据基因突变发生的变异.消灭城市的消灭.激发性突触强度是激发性突触强度.主要神经元的主要神经元.

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