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TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport
Mitochondrial transport along microtubules is mediated by Miro1 and TRAK adaptors that recruit kinesin-1 and dynein-dynactin. To understand how these opposing motors are regulated during mitochondrial transport, we reconstitute the bidirectional transport of Miro1/TRAK along microtubules in vitro. W...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011603/ https://www.ncbi.nlm.nih.gov/pubmed/36914620 http://dx.doi.org/10.1038/s41467-023-36945-8 |
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author | Canty, John T. Hensley, Andrew Aslan, Merve Jack, Amanda Yildiz, Ahmet |
author_facet | Canty, John T. Hensley, Andrew Aslan, Merve Jack, Amanda Yildiz, Ahmet |
author_sort | Canty, John T. |
collection | PubMed |
description | Mitochondrial transport along microtubules is mediated by Miro1 and TRAK adaptors that recruit kinesin-1 and dynein-dynactin. To understand how these opposing motors are regulated during mitochondrial transport, we reconstitute the bidirectional transport of Miro1/TRAK along microtubules in vitro. We show that the coiled-coil domain of TRAK activates dynein-dynactin and enhances the motility of kinesin-1 activated by its cofactor MAP7. We find that TRAK adaptors that recruit both motors move towards kinesin-1’s direction, whereas kinesin-1 is excluded from binding TRAK transported by dynein-dynactin, avoiding motor tug-of-war. We also test the predictions of the models that explain how mitochondrial transport stalls in regions with elevated Ca(2+). Transport of Miro1/TRAK by kinesin-1 is not affected by Ca(2+). Instead, we demonstrate that the microtubule docking protein syntaphilin induces resistive forces that stall kinesin-1 and dynein-driven motility. Our results suggest that mitochondrial transport stalls by Ca(2+)-mediated recruitment of syntaphilin to the mitochondrial membrane, not by disruption of the transport machinery. |
format | Online Article Text |
id | pubmed-10011603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100116032023-03-15 TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport Canty, John T. Hensley, Andrew Aslan, Merve Jack, Amanda Yildiz, Ahmet Nat Commun Article Mitochondrial transport along microtubules is mediated by Miro1 and TRAK adaptors that recruit kinesin-1 and dynein-dynactin. To understand how these opposing motors are regulated during mitochondrial transport, we reconstitute the bidirectional transport of Miro1/TRAK along microtubules in vitro. We show that the coiled-coil domain of TRAK activates dynein-dynactin and enhances the motility of kinesin-1 activated by its cofactor MAP7. We find that TRAK adaptors that recruit both motors move towards kinesin-1’s direction, whereas kinesin-1 is excluded from binding TRAK transported by dynein-dynactin, avoiding motor tug-of-war. We also test the predictions of the models that explain how mitochondrial transport stalls in regions with elevated Ca(2+). Transport of Miro1/TRAK by kinesin-1 is not affected by Ca(2+). Instead, we demonstrate that the microtubule docking protein syntaphilin induces resistive forces that stall kinesin-1 and dynein-driven motility. Our results suggest that mitochondrial transport stalls by Ca(2+)-mediated recruitment of syntaphilin to the mitochondrial membrane, not by disruption of the transport machinery. Nature Publishing Group UK 2023-03-13 /pmc/articles/PMC10011603/ /pubmed/36914620 http://dx.doi.org/10.1038/s41467-023-36945-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Canty, John T. Hensley, Andrew Aslan, Merve Jack, Amanda Yildiz, Ahmet TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport |
title | TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport |
title_full | TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport |
title_fullStr | TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport |
title_full_unstemmed | TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport |
title_short | TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport |
title_sort | trak adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011603/ https://www.ncbi.nlm.nih.gov/pubmed/36914620 http://dx.doi.org/10.1038/s41467-023-36945-8 |
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