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Dynactin functions as both a dynamic tether and brake during dynein-driven motility

Author

Listed:
  • Swathi Ayloo

    (Perelman School of Medicine at the University of Pennsylvania
    School of Arts and Sciences at the University of Pennsylvania)

  • Jacob E. Lazarus

    (Perelman School of Medicine at the University of Pennsylvania)

  • Aditya Dodda

    (University of Massachusetts)

  • Mariko Tokito

    (Perelman School of Medicine at the University of Pennsylvania)

  • E Michael Ostap

    (Perelman School of Medicine at the University of Pennsylvania)

  • Erika L. F. Holzbaur

    (Perelman School of Medicine at the University of Pennsylvania)

Abstract

Dynactin is an essential cofactor for most cellular functions of the microtubule motor cytoplasmic dynein, but the mechanism by which dynactin activates dynein remains unclear. Here we use single molecule approaches to investigate dynein regulation by the dynactin subunit p150Glued. We investigate the formation and motility of a dynein-p150Glued co-complex using dual-colour total internal reflection fluorescence microscopy. p150Glued recruits and tethers dynein to the microtubule in a concentration-dependent manner. Single molecule imaging of motility in cell extracts demonstrates that the CAP-Gly domain of p150Glued decreases the detachment rate of the dynein–dynactin complex from the microtubule and also acts as a brake to slow the dynein motor. Consistent with this important role, two neurodegenerative disease-causing mutations in the CAP-Gly domain abrogate these functions in our assays. Together, these observations support a model in which dynactin enhances the initial recruitment of dynein onto microtubules and promotes the sustained engagement of dynein with its cytoskeletal track.

Suggested Citation

  • Swathi Ayloo & Jacob E. Lazarus & Aditya Dodda & Mariko Tokito & E Michael Ostap & Erika L. F. Holzbaur, 2014. "Dynactin functions as both a dynamic tether and brake during dynein-driven motility," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5807
    DOI: 10.1038/ncomms5807
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