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TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport

Author

Listed:
  • John T. Canty

    (University of California at Berkeley
    Genentech Inc.)

  • Andrew Hensley

    (University of California at Berkeley)

  • Merve Aslan

    (University of California at Berkeley)

  • Amanda Jack

    (University of California at Berkeley)

  • Ahmet Yildiz

    (University of California at Berkeley
    University of California at Berkeley
    University of California at Berkeley)

Abstract

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 Ca2+. Transport of Miro1/TRAK by kinesin-1 is not affected by Ca2+. 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 Ca2+-mediated recruitment of syntaphilin to the mitochondrial membrane, not by disruption of the transport machinery.

Suggested Citation

  • John T. Canty & Andrew Hensley & Merve Aslan & Amanda Jack & Ahmet Yildiz, 2023. "TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36945-8
    DOI: 10.1038/s41467-023-36945-8
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    References listed on IDEAS

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    1. Verena Henrichs & Lenka Grycova & Cyril Barinka & Zuzana Nahacka & Jiri Neuzil & Stefan Diez & Jakub Rohlena & Marcus Braun & Zdenek Lansky, 2020. "Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. Vladislav Belyy & Nathan L Hendel & Alexander Chien & Ahmet Yildiz, 2014. "Cytoplasmic dynein transports cargos via load-sharing between the heads," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
    3. Guillermo López-Doménech & Román Serrat & Serena Mirra & Salvatore D'Aniello & Ildiko Somorjai & Alba Abad & Nathalia Vitureira & Elena García-Arumí & María Teresa Alonso & Macarena Rodriguez-Prados &, 2012. "The Eutherian Armcx genes regulate mitochondrial trafficking in neurons and interact with Miro and Trak2," Nature Communications, Nature, vol. 3(1), pages 1-12, January.
    4. Brigette Y. Monroy & Danielle L. Sawyer & Bryce E. Ackermann & Melissa M. Borden & Tracy C. Tan & Kassandra M. Ori-McKenney, 2018. "Competition between microtubule-associated proteins directs motor transport," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    5. Linas Urnavicius & Clinton K. Lau & Mohamed M. Elshenawy & Edgar Morales-Rios & Carina Motz & Ahmet Yildiz & Andrew P. Carter, 2018. "Cryo-EM shows how dynactin recruits two dyneins for faster movement," Nature, Nature, vol. 554(7691), pages 202-206, February.
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