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.
authors: 1] Developmental Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue New York, New York 10065, USA [2] Program in Biochemistry and Structural Biology, Cell and Developmental Biology, and Molecular Biology, Weill Cornell Graduate School of Medical Sciences, Cornell University, 1300 York Avenue New York, New York 10065, USA.
authors: Mu
authors: M
authors: He
authors: Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue New York, New York 10065, USA.
authors: Radhika
authors: R
authors: Subramanian
authors: Developmental Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue New York, New York 10065, USA.
authors: Fiona
authors: F
authors: Bangs
authors: Cell Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue New York, New York 10065, USA.
authors: Tatiana
authors: T
authors: Omelchenko
authors: 1] Developmental Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue New York, New York 10065, USA [2].
authors: Karel F
authors: KF
authors: Liem
authors: Laboratory of Chemistry and Cell Biology, The Rockefeller University, 1230 York Avenue New York, New York 10065, USA.
authors: Tarun M
authors: TM
authors: Kapoor
authors: Developmental Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue New York, New York 10065, USA.
authors: Kathryn V
authors: KV
authors: Anderson
mesh_terms: D000818:Animals; D054468:Axoneme / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002923:Cilia / Q000737:chemistry / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D041681:NIH 3T3 Cells; D011485:Protein Binding; D021381:Protein Transport; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D053823:Hedgehog Proteins; D011994:Recombinant Proteins; C543639:Kif7 protein, mouse; D016547:Kinesins