KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization
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 mecha...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/72483 |
| _version_ | 1811228037606277120 |
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| author | Rui Zheng Yonglan Du Xintai Wang Tailin Liao Zhe Zhang Na Wang Xiumao Li Ying Shen Lei Shi Jianhong Luo Jun Xia Ziyi Wang Junyu Xu |
| author_facet | Rui Zheng Yonglan Du Xintai Wang Tailin Liao Zhe Zhang Na Wang Xiumao Li Ying Shen Lei Shi Jianhong Luo Jun Xia Ziyi Wang Junyu Xu |
| author_sort | Rui Zheng |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:51:45Z |
| format | Article |
| id | doaj.art-1bbc07117eeb410eab587f28548200ca |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:51:45Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1bbc07117eeb410eab587f28548200ca2022-12-22T03:37:49ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.72483KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerizationRui Zheng0Yonglan Du1Xintai Wang2Tailin Liao3Zhe Zhang4Na Wang5https://orcid.org/0000-0002-1438-1508Xiumao Li6Ying Shen7https://orcid.org/0000-0001-7034-5328Lei Shi8https://orcid.org/0000-0001-8695-3432Jianhong Luo9Jun Xia10https://orcid.org/0000-0001-9308-2188Ziyi Wang11Junyu Xu12https://orcid.org/0000-0002-1911-3553Department 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, ChinaDepartment 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, ChinaNHC 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Physiology and Department of Neurology of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaJNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guanzhou, ChinaDepartment 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, ChinaDivision of Life Science and The Brain and Intelligence Research Institute, The Hong Kong University of Science and Technology, Hong Kong, ChinaInnovative Institute of Basic Medical Sciences of Zhejiang University (Yuhang), Hangzhou, ChinaDepartment 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, ChinaDynamic 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.https://elifesciences.org/articles/72483microtubule depolymerizationspine invasioncognitionlong-term potentiationKIF2C |
| spellingShingle | Rui Zheng Yonglan Du Xintai Wang Tailin Liao Zhe Zhang Na Wang Xiumao Li Ying Shen Lei Shi Jianhong Luo Jun Xia Ziyi Wang Junyu Xu KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization eLife microtubule depolymerization spine invasion cognition long-term potentiation KIF2C |
| title | KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization |
| title_full | KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization |
| title_fullStr | KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization |
| title_full_unstemmed | KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization |
| title_short | KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization |
| title_sort | kif2c regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization |
| topic | microtubule depolymerization spine invasion cognition long-term potentiation KIF2C |
| url | https://elifesciences.org/articles/72483 |
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