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The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment
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The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment
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Journal Article
The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment
2014
Overview
Mammalian Hedgehog (Hh) signal transduction requires a primary cilium, a microtubule-based organelle, and the Gli–Sufu complexes that mediate Hh signalling, which are enriched at cilia tips. Kif7, a kinesin-4 family protein, is a conserved regulator of the Hh signalling pathway and a human ciliopathy protein. Here we show that Kif7 localizes to the cilium tip, the site of microtubule plus ends, where it limits cilium length and controls cilium structure. Purified recombinant Kif7 binds the plus ends of growing microtubules
in vitro
, where it reduces the rate of microtubule growth and increases the frequency of microtubule catastrophe. Kif7 is not required for normal intraflagellar transport or for trafficking of Hh pathway proteins into cilia. Instead, a central function of Kif7 in the mammalian Hh pathway is to control cilium architecture and to create a single cilium tip compartment, where Gli–Sufu activity can be correctly regulated.
Anderson and colleagues report that the kinesin-4 family member Kif7 binds to microtubule plus ends at cilium tips to regulate their length and structure, and to ensure the fidelity of Hedgehog signalling.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
