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驱动蛋白家族成员2A（KIF2A）调节齿状颗粒细胞的发育和出生后海马的神经连接。

KIF2A regulates the development of dentate granule cells and postnatal hippocampal wiring.

作者信息

Homma Noriko, Zhou Ruyun, Naseer Muhammad Imran, Chaudhary Adeel G, Al-Qahtani Mohammed H, Hirokawa Nobutaka

机构信息

Department of Cell Biology and Anatomy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Elife. 2018 Jan 9;7:e30935. doi: 10.7554/eLife.30935.

DOI:10.7554/eLife.30935
PMID:29313800
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5811213/
Abstract

Kinesin super family protein 2A (KIF2A), an ATP-dependent microtubule (MT) destabilizer, regulates cell migration, axon elongation, and pruning in the developing nervous system. KIF2A mutations have recently been identified in patients with malformed cortical development. However, postnatal KIF2A is continuously expressed in the hippocampus, in which new neurons are generated throughout an individual's life in established neuronal circuits. In this study, we investigated KIF2A function in the postnatal hippocampus by using tamoxifen-inducible conditional knockout (-cKO) mice. Despite exhibiting no significant defects in neuronal proliferation or migration, -cKO mice showed signs of an epileptic hippocampus. In addition to mossy fiber sprouting, the -cKO dentate granule cells (DGCs) showed , leading to the growth of many aberrant overextended dendrites that eventually developed axonal properties. These results suggested that postnatal KIF2A is a key length regulator of DGC developing neurites and is involved in the establishment of precise postnatal hippocampal wiring.

摘要

驱动蛋白超家族蛋白2A（KIF2A）是一种依赖ATP的微管（MT）解聚蛋白，在发育中的神经系统中调节细胞迁移、轴突伸长和修剪。最近在皮质发育畸形患者中发现了KIF2A突变。然而，出生后KIF2A在海马体中持续表达，在已建立的神经回路中，个体一生中都会在海马体中产生新的神经元。在本研究中，我们通过使用他莫昔芬诱导的条件性敲除（-cKO）小鼠来研究出生后海马体中KIF2A的功能。尽管-cKO小鼠在神经元增殖或迁移方面没有表现出明显缺陷，但却表现出海马体癫痫的迹象。除了苔藓纤维出芽外，-cKO齿状颗粒细胞（DGC）还表现出 ，导致许多异常过度延伸的树突生长，最终发展出轴突特性。这些结果表明，出生后KIF2A是DGC发育中神经突的关键长度调节因子，并参与出生后海马体精确布线的建立。 （注：原文中“the -cKO dentate granule cells (DGCs) showed ”后面似乎缺失了部分内容）

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/78621c6aab09/elife-30935-fig7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/78621c6aab09/elife-30935-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/340f572c8098/elife-30935-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/42216999e517/elife-30935-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/84ec10b4c1c7/elife-30935-fig2-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/5463c21ed922/elife-30935-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/72387b16f177/elife-30935-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/328e1b2947ed/elife-30935-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/f585d682383b/elife-30935-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/52d13a983968/elife-30935-fig6-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23c7/5811213/78621c6aab09/elife-30935-fig7.jpg

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