中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (1): 209-223.doi: 10.4103/1673-5374.391301

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

KIF21A与KANK1相互作用调节神经元树突形态和突触的可塑性

  

  • 出版日期:2025-01-15 发布日期:2025-01-15
  • 基金资助:
    国家重点研发计划项目（2021ZD0202503）；国家自然科学基金项目（31872759和32070707）；深圳市科技计划项目（RCJC20210609104333007）；深港脑科学创新研究院开发项目（2021SHIBS002）

The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

Shi-Yan Sun1, 2, Lingyun Nie1, 3, Jing Zhang4, 5, Xue Fang1, Hongmei Luo1, 2, Chuanhai Fu1, 3, Zhiyi Wei4, 5, Ai-Hui Tang1, 2, *   

  1. 1Hefei National Research Center for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, Ministry of Education Key Laboratory for Membrane-less Organelles and Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China; 2Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, Anhui Province, China; 3CAS Center for Excellence in Molecular Cell Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China; 4Department of Neurobiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong Province, China; 5Brain Research Center, Southern University of Science and Technology, Shenzhen, Guangdong Province, China
  • Online:2025-01-15 Published:2025-01-15
  • Contact: Ai-Hui Tang, PhD, tangah@ustc.edu.cn.
  • Supported by:
    This study was supported by the National Key Research and Development Program of China, No. 2021ZD0202503 (to AHT); the National Natural Science Foundation of China, Nos. 31872759 (to AHT) and 32070707 (to CF); Shenzhen Science and Technology Program, No. RCJC20210609104333007 (to ZW); and Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Fundamental Research Institutions, No. 2021SHIBS0002 (to ZW).

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摘要：

树突棘的形态变化与神经元之间功能性交流的改变有关，而神经元之间的功能性交流是学习和记忆的基础。研究发现，Kinesin-4亚家族成员KIF21A可通过与KANK1相互作用，参与组织细胞边缘微管-肌动蛋白网络，但KIF21A是否也会调节神经元的树突结构和功能尚不清楚。实验首先发现KIF21A存在于部分树突棘，且含有KIF21A的树突棘比不含的树突棘尺寸更大，且具有更强的化学诱导长时程增强作用。而后发现，KIF21A-KANK1相互作用是树突棘形态发生和突触可塑性所必需的。敲低KIF21A或KANK1可抑制树突棘形态发生和树突分支，这种调节依赖于KIF21A和KANK1之间的直接结合。进一步在大鼠海马中敲低KIF21A，可抑制高频刺激引起的长时程增强受到抑制以及动物的认知能力。上述结果揭示了KIF21A在树突形态和突触功能调节中的功能。

https://orcid.org/0000-0003-3715-6714 (Ai-Hui Tang); https://orcid.org/0000-0002-4446-6502 (Zhiyi Wei); 
https://orcid.org/0000-0003-4354-3796 (Chuanhai Fu)

关键词: KIF21A, KANK1, 树突棘, 树突, 树突棘形态, 细胞骨架, 肌动蛋白, talin1, 微管, 突触可塑性

Abstract: Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory. Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1; however, whether KIF21A modulates dendritic structure and function in neurons remains unknown. In this study, we found that KIF21A was distributed in a subset of dendritic spines, and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines. Furthermore, the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity. Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching, and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1, but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1. Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’ cognitive abilities. Taken together, our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

Key words: actin, cytoskeleton, dendrite, KANK1, KIF21A, microtubule, spine morphology, spine, synaptic plasticity, talin1