Details

Autor(en) / Beteiligte

• Jiang, Shuo
• Mani, Nandini
• Wilson-Kubalek, Elizabeth M.
• Ku, Pei-I
• Milligan, Ronald A.
• Subramanian, Radhika

Titel

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

Ist Teil von

• Developmental cell, 2019-06, Vol.49 (5), p.711-730.e8

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •Kif7 recognizes microtubule ends through preferential binding to GTP over GDP-tubulin•ATP hydrolysis enhances the discrimination between GTP- and GDP-tubulin by Kif7•Structural alterations in the motor domain underlie Kif7’s atypical mechanochemistry•Kif7 modulates tubulin mechanochemistry to promote its own microtubule binding The ciliary kinesin Kif7 acts at the distal tip of the primary cilium during Hh signaling and ciliogenesis. Jiang et al. examine how this non-motile kinesin recognizes microtubule plus ends. They report that Kif7 recognizes GTP-like tubulin and regulates the tubulin mechanochemical cycle to maintain its association with microtubule ends.