title: KIF13B establishes a CAV1-enriched microdomain at the ciliary transition zone to promote Sonic hedgehog signalling.
abstract: Ciliary membrane composition is controlled by transition zone (TZ) proteins such as RPGRIP1, RPGRIPL and NPHP4, which are vital for balanced coordination of diverse signalling systems like the Sonic hedgehog (Shh) pathway. Activation of this pathway involves Shh-induced ciliary accumulation of Smoothened (SMO), which is disrupted by disease-causing mutations in TZ components. Here we identify kinesin-3 motor protein KIF13B as a novel member of the RPGRIP1N-C2 domain-containing protein family and show that KIF13B regulates TZ membrane composition and ciliary SMO accumulation. KIF13B is upregulated during ciliogenesis and is recruited to the ciliary base by NPHP4, which binds to two distinct sites in the KIF13B tail region, including an RPGRIP1N-C2 domain. KIF13B and NPHP4 are both essential for establishment of a CAV1 membrane microdomain at the TZ, which in turn is required for Shh-induced ciliary SMO accumulation. Thus KIF13B is a novel regulator of ciliary TZ configuration, membrane composition and Shh signalling.
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Schou
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Johanne B
authors.initials: JB
authors.lastname: Mogensen
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Stine K
authors.initials: SK
authors.lastname: Morthorst
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Brian S
authors.initials: BS
authors.lastname: Nielsen
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Aiste
authors.initials: A
authors.lastname: Aleliunaite
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, CH Utrecht 3584, The Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Serra-Marques
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Nicoline
authors.initials: N
authors.lastname: Fürstenberg
authors.affiliation: Inserm UMR-1163, Laboratory of Hereditary Kidney diseases, Paris 75015, France.|Paris Descartes Sorbonne Paris Cité University, Imagine Institut, Paris 75015, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Saunier
authors.affiliation: Inserm UMR-1163, Laboratory of Hereditary Kidney diseases, Paris 75015, France.|Paris Descartes Sorbonne Paris Cité University, Imagine Institut, Paris 75015, France.
authors.forename: Albane A
authors.initials: AA
authors.lastname: Bizet
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Iben R
authors.initials: IR
authors.lastname: Veland
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, CH Utrecht 3584, The Netherlands.
authors.forename: Anna
authors.identifier: 0000-0002-9048-8614
authors.initials: A
authors.lastname: Akhmanova
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Søren T
authors.initials: ST
authors.lastname: Christensen
authors.affiliation: Department of Biology, Section of Cell Biology and Physiology, The August Krogh Building, University of Copenhagen, Universitetsparken 13, Copenhagen OE DK-2100, Denmark.
authors.forename: Lotte B
authors.identifier: 0000-0002-9749-3758
authors.initials: LB
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D002923:Cilia / Q000502:physiology*; D019295:Computational Biology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D000072417:Protein Domains / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000072086:Smoothened Receptor / Q000378:metabolism*; D015854:Up-Regulation; D000071676:Zinc Finger Protein GLI1 / Q000235:genetics / Q000378:metabolism
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D008565:Membrane Proteins; C491578:NPHP4 protein, human; C559479:NPHP4 protein, mouse; D011506:Proteins; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1; C513406:KIF13B protein, human; C587627:KIF13b protein, mouse; D016547:Kinesins