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PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport

Author

Listed:
  • Nida Siddiqui

    (University of Warwick
    University of Warwick)

  • Alexander James Zwetsloot

    (University of Warwick
    Warwick Medical School)

  • Alice Bachmann

    (University of Warwick
    University of Warwick)

  • Daniel Roth

    (University of Warwick
    University of Warwick)

  • Hamdi Hussain

    (University of Warwick
    University of Warwick)

  • Jonathan Brandt

    (University of Warwick
    University of Warwick)

  • Irina Kaverina

    (Vanderbilt University Medical Center)

  • Anne Straube

    (University of Warwick
    University of Warwick)

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.

Suggested Citation

  • Nida Siddiqui & Alexander James Zwetsloot & Alice Bachmann & Daniel Roth & Hamdi Hussain & Jonathan Brandt & Irina Kaverina & Anne Straube, 2019. "PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10644-9
    DOI: 10.1038/s41467-019-10644-9
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    Cited by:

    1. Ryan P. Hildebrandt & Kathryn R. Moss & Aleksandra Janusz-Kaminska & Luke A. Knudson & Lance T. Denes & Tanvi Saxena & Devi Prasad Boggupalli & Zhuangyue Li & Kun Lin & Gary J. Bassell & Eric T. Wang, 2023. "Muscleblind-like proteins use modular domains to localize RNAs by riding kinesins and docking to membranes," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Wenjuan Wang & Jinqi Ren & Weiye Song & Yong Zhang & Wei Feng, 2022. "The architecture of kinesin-3 KLP-6 reveals a multilevel-lockdown mechanism for autoinhibition," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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