Interplay between the Kinesin and Tubulin Mechanochemical Cycles Underlies Microtubule Tip Tracking by the Non-motile Ciliary Kinesin Kif7

Dev Cell. 2019 Jun 3;49(5):711-730.e8. doi: 10.1016/j.devcel.2019.04.001. Epub 2019 Apr 25.


The correct localization of Hedgehog effectors to the tip of primary cilia is critical for proper signal transduction. The conserved non-motile kinesin Kif7 defines a "cilium-tip compartment" by localizing to the distal ends of axonemal microtubules. How Kif7 recognizes microtubule ends remains unknown. We find that Kif7 preferentially binds GTP-tubulin at microtubule ends over GDP-tubulin in the mature microtubule lattice, and ATP hydrolysis by Kif7 enhances this discrimination. Cryo-electron microscopy (cryo-EM) structures suggest that a rotated microtubule footprint and conformational changes in the ATP-binding pocket underlie Kif7's atypical microtubule-binding properties. Finally, Kif7 not only recognizes but also stabilizes a GTP-form of tubulin to promote its own microtubule-end localization. Thus, unlike the characteristic microtubule-regulated ATPase activity of kinesins, Kif7 modulates the tubulin mechanochemical cycle. We propose that the ubiquitous kinesin fold has been repurposed in Kif7 to facilitate organization of a spatially restricted platform for localization of Hedgehog effectors at the cilium tip.

Keywords: Hedgehog; Kif7; cilia; cilium tip; cryo-EM; kinesin; mechanochemistry; microtubule; tip-tracking; tubulin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cilia / physiology*
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Kinesins / chemistry
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Mechanotransduction, Cellular*
  • Microtubules / metabolism*
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Signal Transduction
  • Tubulin / genetics
  • Tubulin / metabolism*


  • KIF7 protein, human
  • Tubulin
  • Guanosine Triphosphate
  • Kinesins