KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization
| Autor: | Yonglan Du, Rui Zheng, Xintai Wang, Tailin Liao, Zhe Zhang, Na Wang, Xiumao Li, Ying Shen, Lei Shi, Jianhong Luo, Jun Xia, Ziyi Wang, Junyu Xu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
QH301-705.5 Science Long-Term Potentiation Kinesins spine invasion Microtubules General Biochemistry Genetics and Molecular Biology Mice Cognition Animals Humans Receptors AMPA microtubule depolymerization Biology (General) Neurons KIF2C Neuronal Plasticity General Immunology and Microbiology General Neuroscience General Medicine Mice Inbred C57BL Protein Transport HEK293 Cells Synapses Medicine Female |
| Zdroj: | eLife, Vol 11 (2022) |
| ISSN: | 2050-084X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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