PLOS Genetics
Abstract
The UNC-104/KIF1A motor is crucial for axonal transport of synaptic vesicles, but how the UNC-104/KIF1A motor is activatedin vivois not fully understood. Here, we identified point mutations located in the motor domain or the inhibitory CC1 domain, which resulted in gain-of-function alleles ofunc-104that exhibit hyperactive axonal transport and abnormal accumulation of synaptic vesicles. In contrast to the cell body localization of wild type motor, the mutant motors accumulate on neuronal processes. Once on the neuronal process, the mutant motors display dynamic movement similarly to wild type motors. The gain-of-function mutation on the motor domain leads to an active dimeric conformation, releasing the inhibitory CC1 region from the motor domain. Genetically engineered mutations in the motor domain or CC1 of UNC-104, which disrupt the autoinhibitory interface, also led to the gain of function and hyperactivation of axonal transport. Thus, the CC1/motor domain-mediated autoinhibition is crucial for UNC-104/KIF1A-mediated axonal transportin vivo.
| 论文编号: | DOI:10.1371/journal.pgen.1009940 |
| 论文题目: | Motor Domain-Mediated Autoinhibition Dictates Axonal Transport by the Kinesin UNC-104/KIF1A |
| 英文论文题目: | Motor Domain-Mediated Autoinhibition Dictates Axonal Transport by the Kinesin UNC-104/KIF1A |
| 第一作者: | Dezi Cong, Jinqi Ren, Yurong Zhou, Shuang Wang, Jingjing Liang, Mei Ding, Wei Feng |
| 英文第一作者: | Dezi Cong, Jinqi Ren, Yurong Zhou, Shuang Wang, Jingjing Liang, Mei Ding, Wei Feng |
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| 发表年度: | 2021-12-02 |
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| 摘要: | The UNC-104/KIF1A motor is crucial for axonal transport of synaptic vesicles, but how the UNC-104/KIF1A motor is activatedin vivois not fully understood. Here, we identified point mutations located in the motor domain or the inhibitory CC1 domain, which resulted in gain-of-function alleles ofunc-104that exhibit hyperactive axonal transport and abnormal accumulation of synaptic vesicles. In contrast to the cell body localization of wild type motor, the mutant motors accumulate on neuronal processes. Once on the neuronal process, the mutant motors display dynamic movement similarly to wild type motors. The gain-of-function mutation on the motor domain leads to an active dimeric conformation, releasing the inhibitory CC1 region from the motor domain. Genetically engineered mutations in the motor domain or CC1 of UNC-104, which disrupt the autoinhibitory interface, also led to the gain of function and hyperactivation of axonal transport. Thus, the CC1/motor domain-mediated autoinhibition is crucial for UNC-104/KIF1A-mediated axonal transportin vivo. |
| 英文摘要: | The UNC-104/KIF1A motor is crucial for axonal transport of synaptic vesicles, but how the UNC-104/KIF1A motor is activatedin vivois not fully understood. Here, we identified point mutations located in the motor domain or the inhibitory CC1 domain, which resulted in gain-of-function alleles ofunc-104that exhibit hyperactive axonal transport and abnormal accumulation of synaptic vesicles. In contrast to the cell body localization of wild type motor, the mutant motors accumulate on neuronal processes. Once on the neuronal process, the mutant motors display dynamic movement similarly to wild type motors. The gain-of-function mutation on the motor domain leads to an active dimeric conformation, releasing the inhibitory CC1 region from the motor domain. Genetically engineered mutations in the motor domain or CC1 of UNC-104, which disrupt the autoinhibitory interface, also led to the gain of function and hyperactivation of axonal transport. Thus, the CC1/motor domain-mediated autoinhibition is crucial for UNC-104/KIF1A-mediated axonal transportin vivo. |
| 刊物名称: | PLOS Genetics |
| 英文刊物名称: | PLOS Genetics |
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| 其它备注: | Dezi Cong, Jinqi Ren, Yurong Zhou, Shuang Wang, Jingjing Liang, Mei Ding, Wei Feng. Motor Domain-Mediated Autoinhibition Dictates Axonal Transport by the Kinesin UNC-104/KIF1A. PLOS Genetics. DOI:10.1371/journal.pgen.1009940 |
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