KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization

eLife

Zhe Zhang¹  Na Wang¹  Junyu Xu¹  Rui Zheng¹  Yonglan Du¹  Tailin Liao¹  Jianhong Luo¹  Xiumao Li²  Ying Shen³  Jun Xia⁴  Ziyi Wang⁵  Lei Shi⁶  Xintai Wang⁷ 

[1] 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;Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Department of Physiology and Department of Neurology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China;Division of Life Science and The Brain and Intelligence Research Institute, The Hong Kong University of Science and Technology, Hong Kong, China;Innovative Institute of Basic Medical Sciences of Zhejiang University (Yuhang), Hangzhou, China;JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guanzhou, 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;

关键词: microtubule depolymerization;    spine invasion;    cognition;    long-term potentiation;    KIF2C;    Mouse;   

DOI  :  10.7554/eLife.72483

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY