Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory
- University of Hong Kong, Hong Kong
- Chinese University of Hong Kong, Hong Kong
Abstract
The kinesin I family of motor proteins are crucial for axonal transport, but their roles in dendritic transport and postsynaptic function are not well-defined. Gene duplication and subsequent diversification give rise to three homologous kinesin I proteins (KIF5A, KIF5B and KIF5C) in vertebrates, but it is not clear whether and how they exhibit functional specificity. Here we show that knockdown of KIF5A or KIF5B differentially affects excitatory synapses and dendritic transport in hippocampal neurons. The functional specificities of the two kinesins are determined by their diverse carboxyl-termini, where arginine methylation occurs in KIF5B and regulates its function. KIF5B conditional knockout mice exhibit deficits in dendritic spine morphogenesis, synaptic plasticity and memory formation. Our findings provide insights into how expansion of the kinesin I family during evolution leads to diversification and specialization of motor proteins in regulating postsynaptic function.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Research Grant Council of Hong Kong (GRF 16100814)
- Kwok-On Lai
Shenzhen Peacock Team Project (KQTD2015033117210153)
- Jiandong Huang
Shenzhen Science Technology Innovation Committee Basic Science Research Grant (JCYJ20170413154523577)
- Jiandong Huang
University Grants Committee of Hong Kong (AoE/M-604/16)
- Wing-Ho Yung
University Grants Committee of Hong Kong (T13-605/18-W)
- Kwok-On Lai
Research Grant Council of Hong Kong (GRF 17135816)
- Kwok-On Lai
Research Grant Council of Hong Kong (GRF 17106018)
- Kwok-On Lai
Research Grant Council of Hong Kong (ECS 27119715)
- Kwok-On Lai
University Grants Committee of Hong Kong (AoE/M-604/16)
- Kwok-On Lai
Research Grant Council of Hong Kong (ECS 27103715)
- Cora Sau Wan Lai
Research Grant Council of Hong Kong (GRF 17128816)
- Cora Sau Wan Lai
National Natural Science Foundation of China (NSFC/General Program 31571031)
- Cora Sau Wan Lai
Health and Medical Research Fund Hong Kong (03143096)
- Cora Sau Wan Lai
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were approved and performed in accordance with University of Hong Kong Committee on the Use of Live Animals (CULATR 3935-16 and CULATR 4056-16) and in Teaching and Research guidelines.
Copyright
© 2020, Zhao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Specific depletion of the motor protein KIF5B leads to deficits in dendritic transport, synaptic plasticity and memory
eLife 9:e53456.
https://doi.org/10.7554/eLife.53456
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