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PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport
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Siddiqui, Nida, Zwetsloot, Alexander J., Bachmann, Alice, Roth, Daniel, Hussain, Hamdi, Brandt, Jonathan, Kaverina, Irina and Straube, Anne (2019) PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport. Nature Communications, 10 . 2693 . doi:10.1038/s41467-019-10644-9 ISSN 2041-1723.
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Official URL: https://doi.org/10.1038/s41467-019-10644-9
Abstract
The kinesin-3 KIF1C is a fast organelle transporter implicated in the transport of dense core vesicles in neurons and the delivery of integrins to cell adhesions. Here we report the mechanisms of autoinhibition and release that control the activity of KIF1C. We show that the microtubule binding surface of KIF1C motor domain interacts with its stalk and that these autoinhibitory interactions are released upon binding of protein tyrosine phosphatase PTPN21. The FERM domain of PTPN21 stimulates dense core vesicle transport in primary hippocampal neurons and rescues integrin trafficking in KIF1C-depleted cells. In vitro, human full-length KIF1C is a processive, plus-end directed motor. Its landing rate onto microtubules increases in the presence of either PTPN21 FERM domain or the cargo adapter Hook3 that binds the same region of KIF1C tail. This autoinhibition release mechanism allows cargo-activated transport and might enable motors to participate in bidirectional cargo transport without undertaking a tug-of-war.
| Item Type: | Journal Article | |||||||||||||||||||||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Kinesin, Kinesin -- Movements, Cell organelles, Integrins, Cell adhesion, Microtubules | |||||||||||||||||||||||||||
| Journal or Publication Title: | Nature Communications | |||||||||||||||||||||||||||
| Publisher: | Nature Publishing Group | |||||||||||||||||||||||||||
| ISSN: | 2041-1723 | |||||||||||||||||||||||||||
| Official Date: | 19 June 2019 | |||||||||||||||||||||||||||
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| Volume: | 10 | |||||||||||||||||||||||||||
| Article Number: | 2693 | |||||||||||||||||||||||||||
| DOI: | 10.1038/s41467-019-10644-9 | |||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||||||||
| Date of first compliant deposit: | 10 July 2019 | |||||||||||||||||||||||||||
| Date of first compliant Open Access: | 17 July 2019 | |||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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