The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment Journal Article

   


Authors: He, M.; Subramanian, R.; Bangs, F.; Omelchenko, T.; Liem, K. F. Jr; Kapoor, T. M.; Anderson, K. V.
Article Title: The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment
Abstract: 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. © 2014 Macmillan Publishers Limited. All rights reserved.
Keywords: signal transduction; controlled study; unclassified drug; human cell; nonhuman; protein function; protein localization; animal cell; mouse; mammalia; embryo; sonic hedgehog protein; protein binding; in vitro study; recombinant protein; protein transport; adenosine triphosphatase; microtubule; erinaceidae; eukaryotic flagellum; ciliary motility; axoneme; human; priority journal; article; protein kif7
Journal Title: Nature Cell Biology
Volume: 16
Issue: 7
ISSN: 1465-7392
Publisher: Nature Publishing Group  
Date Published: 2014-07-01
Start Page: 663
End Page: 672
Language: English
DOI: 10.1038/ncb2988
PROVIDER: scopus
PMCID: PMC4085576
PUBMED: 24952464
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84903701173&partnerID=40&md5=0c86d1b72b3191c50aa1e69b8da8cc85
Notes: Cited By (since 1996):1 -- Export Date: 1 August 2014 -- CODEN: NCBIF -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Karel F Liem
    12 Liem
  2. Kathryn Anderson
    148 Anderson
  3. Tatiana A Omelchenko
    19 Omelchenko
  4. Fiona Kathlen Bangs
    4 Bangs
  5. Mu He
    6 He
Related MSK Work