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

Adam R. Fenton, Thomas A. Jongens () and Erika L. F. Holzbaur ()
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Adam R. Fenton: University of Pennsylvania Perelman School of Medicine
Thomas A. Jongens: University of Pennsylvania Perelman School of Medicine
Erika L. F. Holzbaur: University of Pennsylvania Perelman School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-24862-7

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