Zheng Rui, Du Yonglan, Wang Xintai, Liao Tailin, Zhang Zhe, Wang Na, Li Xiumao, Shen Ying, Shi Lei, Luo Jianhong, Xia Jun, Wang Ziyi, Xu Junyu
Department of Neurobiology and Department of Rehabilitation of the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
NHC and CAMS Key Laboratory of Medical Neurobiology, Ministry of Education Frontier Science Center for Brain Research and Brain Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, China.
Elife. 2022 Feb 9;11:e72483. doi: 10.7554/eLife.72483.
Dynamic microtubules play a critical role in cell structure and function. In nervous system, microtubules are the major route for cargo protein trafficking and they specially extend into and out of synapses to regulate synaptic development and plasticity. However, the detailed depolymerization mechanism that regulates dynamic microtubules in synapses and dendrites is still unclear. In this study, we find that KIF2C, a dynamic microtubule depolymerization protein without known function in the nervous system, plays a pivotal role in the structural and functional plasticity of synapses and regulates cognitive function in mice. Through its microtubule depolymerization capability, KIF2C regulates microtubule dynamics in dendrites, and regulates microtubule invasion of spines in neurons in a neuronal activity-dependent manner. Using RNAi knockdown and conditional knockout approaches, we showed that KIF2C regulates spine morphology and synaptic membrane expression of AMPA receptors. Moreover, KIF2C deficiency leads to impaired excitatory transmission, long-term potentiation, and altered cognitive behaviors in mice. Collectively, our study explores a novel function of KIF2C in the nervous system and provides an important regulatory mechanism on how activity-dependent microtubule dynamic regulates synaptic plasticity and cognition behaviors.
动态微管在细胞结构和功能中发挥着关键作用。在神经系统中，微管是货物蛋白运输的主要途径，它们特别延伸到突触内外以调节突触发育和可塑性。然而，调节突触和树突中动态微管的详细解聚机制仍不清楚。在本研究中，我们发现KIF2C，一种在神经系统中功能未知的动态微管解聚蛋白，在突触的结构和功能可塑性中起关键作用，并调节小鼠的认知功能。通过其微管解聚能力，KIF2C调节树突中的微管动力学，并以神经元活动依赖的方式调节神经元中棘突的微管侵入。使用RNAi敲低和条件性敲除方法，我们表明KIF2C调节AMPA受体的棘突形态和突触膜表达。此外，KIF2C缺乏导致小鼠兴奋性传递受损、长时程增强和认知行为改变。总之，我们的研究探索了KIF2C在神经系统中的新功能，并提供了一个重要的调节机制，即活动依赖的微管动态如何调节突触可塑性和认知行为。
