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Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A
The UNC-104/KIF1A motor is crucial for axonal transport of synaptic vesicles, but how the UNC-104/KIF1A motor is activated in vivo is 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 of unc-...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659337/ https://www.ncbi.nlm.nih.gov/pubmed/34843479 http://dx.doi.org/10.1371/journal.pgen.1009940 |
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author | Cong, Dezi Ren, Jinqi Zhou, Yurong Wang, Shuang Liang, Jingjing Ding, Mei Feng, Wei |
author_facet | Cong, Dezi Ren, Jinqi Zhou, Yurong Wang, Shuang Liang, Jingjing Ding, Mei Feng, Wei |
author_sort | Cong, Dezi |
collection | PubMed |
description | The UNC-104/KIF1A motor is crucial for axonal transport of synaptic vesicles, but how the UNC-104/KIF1A motor is activated in vivo is 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 of unc-104 that 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 transport in vivo. |
format | Online Article Text |
id | pubmed-8659337 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-86593372021-12-10 Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A Cong, Dezi Ren, Jinqi Zhou, Yurong Wang, Shuang Liang, Jingjing Ding, Mei Feng, Wei PLoS Genet Research Article The UNC-104/KIF1A motor is crucial for axonal transport of synaptic vesicles, but how the UNC-104/KIF1A motor is activated in vivo is 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 of unc-104 that 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 transport in vivo. Public Library of Science 2021-11-29 /pmc/articles/PMC8659337/ /pubmed/34843479 http://dx.doi.org/10.1371/journal.pgen.1009940 Text en © 2021 Cong et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Cong, Dezi Ren, Jinqi Zhou, Yurong Wang, Shuang Liang, Jingjing Ding, Mei Feng, Wei Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A |
title | Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A |
title_full | Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A |
title_fullStr | Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A |
title_full_unstemmed | Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A |
title_short | Motor domain-mediated autoinhibition dictates axonal transport by the kinesin UNC-104/KIF1A |
title_sort | motor domain-mediated autoinhibition dictates axonal transport by the kinesin unc-104/kif1a |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659337/ https://www.ncbi.nlm.nih.gov/pubmed/34843479 http://dx.doi.org/10.1371/journal.pgen.1009940 |
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