Control of the initiation and termination of kinesin-1-driven transport by myosin-Ic and nonmuscle tropomyosin

Curr Biol. 2015 Feb 16;25(4):523-9. doi: 10.1016/j.cub.2014.12.008. Epub 2015 Feb 5.


Intracellular transport is largely driven by processive microtubule- and actin-based molecular motors. Nonprocessive motors have also been localized to trafficking cargos, but their roles are not well understood. Myosin-Ic (Myo1c), a nonprocessive actin motor, functions in a variety of exocytic events, although the underlying mechanisms are not yet clear. To investigate the interplay between myosin-I and the canonical long-distance transport motor kinesin-1, we attached both motor types to lipid membrane-coated bead cargo, using an attachment strategy that allows motors to actively reorganize within the membrane in response to the local cytoskeletal environment. We compared the motility of kinesin-1-driven cargos in the absence and presence of Myo1c at engineered actin/microtubule intersections. We found that Myo1c significantly increases the frequency of kinesin-1-driven microtubule-based runs that begin at actin/microtubule intersections. Myo1c also regulates the termination of processive runs. Beads with both motors bound have a significantly higher probability of pausing at actin/microtubule intersections, remaining tethered for an average of 20 s, with some pauses lasting longer than 200 s. The actin-binding protein nonmuscle tropomyosin (Tm) provides spatially specific regulation of interactions between myosin motors and actin filaments in vivo; in the crossed-filament in vitro assay, we found that Tm2-actin abolishes Myo1c-specific effects on both run initiation and run termination. Together, these observations suggest Myo1c is important for the selective initiation and termination of kinesin-1-driven runs along microtubules at specific actin filament populations within the cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement
  • Cytoskeleton / metabolism*
  • Humans
  • Kinesin / genetics*
  • Kinesin / metabolism
  • Myosin Type I / genetics*
  • Myosin Type I / metabolism
  • Protein Transport
  • Tropomyosin / genetics*
  • Tropomyosin / metabolism


  • KIF5B protein, human
  • TPM2 protein, human
  • Tropomyosin
  • Myosin Type I
  • MYO1C protein, human
  • Kinesin