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KCTD10通过破坏大脑疾病相关蛋白KCTD13的稳定性来调节大脑发育

Jianbo Cheng¹, Zhen Wang¹, Manpei Tang¹

¹Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, Key Lab of Rare Pediatric Diseases of Ministry of Education, School of Life Sciences, Central South University, Changsha, Hunan 410078, China.

Proceedings of the National Academy of Sciences of the United States of America

|March 15, 2024

概括

含有10 (KCTD10) 的通道四重化域调节神经元前体发育和大脑大小. KCTD10 缺陷通过增加 KCTD13 水平导致运动缺陷,影响神经发育.

科学领域:

神经科学是一个神经科学.
发展生物学发展生物学
分子生物学分子生物学

背景情况:

该KCTD (通道四重化域) 家族与神经精神疾病有关.
在大脑发育和疾病中的KCTD10的特定功能在很大程度上是未知的.

研究的目的:

阐明KCTD10在大脑发育中的生理作用.
研究KCTD10的功能和它与神经发育障碍的联系背后的分子机制.

主要方法:

在发育中的大脑中分析KCTD10表达.
产生和分析Kctd10缺乏的小鼠模型.
鉴定和描述与KCTD10相互作用的蛋白质,包括KCTD13.
评估KCTD13在神经元原生细胞中的作用.
评估Kctd10淘汰赛小鼠的运动功能.

主要成果:

在大脑发育过程中,KCTD10在神经元原生和层V神经元中高度表达.
Kctd10 缺乏导致异常的原始细胞增殖/分化,深层神经元减少,上层神经元增加,以及大脑尺寸缩小.
KCTD10与KCTD13相互作用,并调解其依赖于无处不在的降解.
切除KCTD10会增加KCTD13水平,导致类似于KCTD10缺陷的表型.
Kctd10 淘汰赛小鼠表现出运动缺陷.

结论:

KCTD10在调节神经元前体发育和大脑大小方面发挥着至关重要的作用.
KCTD10的功能部分通过KCTD13的降解来调节.
这项研究为涉及KCTD10和KCTD13的神经发育障碍的病变产生提供了洞察力.

关键词:

KCTD10 KCTD10 的意思是 KCTD13 的时间.皮层神经发生是皮层神经发生.运动缺陷运动缺陷随处可见的依赖性降解降解.

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