Mitochondrial adaptor TRAK2 activates and functionally links opposing kinesin and dynein motors.

Adam R Fenton, Thomas A Jongens, Erika L F Holzbaur

Nature communications 2021 Jul 28

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Mitochondria are transported along microtubules by opposing kinesin and dynein motors. Kinesin-1 and dynein-dynactin are linked to mitochondria by TRAK proteins, but it is unclear how TRAKs coordinate these motors. We used single-molecule imaging of cell lysates to show that TRAK2 robustly activates kinesin-1 for transport toward the microtubule plus-end. TRAK2 is also a novel dynein activating adaptor that utilizes a conserved coiled-coil motif to interact with dynein to promote motility toward the microtubule minus-end. However, dynein-mediated TRAK2 transport is minimal unless the dynein-binding protein LIS1 is present at a sufficient level. Using co-immunoprecipitation and co-localization experiments, we demonstrate that TRAK2 forms a complex containing both kinesin-1 and dynein-dynactin. These motors are functionally linked by TRAK2 as knockdown of either kinesin-1 or dynein-dynactin reduces the initiation of TRAK2 transport toward either microtubule end. We propose that TRAK2 coordinates kinesin-1 and dynein-dynactin as an interdependent motor complex, providing integrated control of opposing motors for the proper transport of mitochondria. © 2021. The Author(s).

Citation

Adam R Fenton, Thomas A Jongens, Erika L F Holzbaur. Mitochondrial adaptor TRAK2 activates and functionally links opposing kinesin and dynein motors. Nature communications. 2021 Jul 28;12(1):4578