title: Pitchfork and Gprasp2 Target Smoothened to the Primary Cilium for Hedgehog Pathway Activation.
abstract: The seven-transmembrane receptor Smoothened (Smo) activates all Hedgehog (Hh) signaling by translocation into the primary cilia (PC), but how this is regulated is not well understood. Here we show that Pitchfork (Pifo) and the G protein-coupled receptor associated sorting protein 2 (Gprasp2) are essential components of an Hh induced ciliary targeting complex able to regulate Smo translocation to the PC. Depletion of Pifo or Gprasp2 leads to failure of Smo translocation to the PC and lack of Hh target gene activation. Together, our results identify a novel protein complex that is regulated by Hh signaling and required for Smo ciliary trafficking and Hh pathway activation.
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, München-Neuherberg, Germany.|Institute of Stem Cell Research, Helmholtz Zentrum München, München-Neuherberg, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Bomi
authors.initials: B
authors.lastname: Jung
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, München-Neuherberg, Germany.|Institute of Stem Cell Research, Helmholtz Zentrum München, München-Neuherberg, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Padula
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, München-Neuherberg, Germany.|Institute of Stem Cell Research, Helmholtz Zentrum München, München-Neuherberg, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Burtscher
authors.affiliation: Institute of Computational Biology, Helmholtz Zentrum München, München-Neuherberg, Germany.|Department of Ecology & Evolutionary Biology, University of Tennessee, Knoxville TN 37996, United States of America.
authors.forename: Cedric
authors.initials: C
authors.lastname: Landerer
authors.affiliation: Institute of Computational Biology, Helmholtz Zentrum München, München-Neuherberg, Germany.|Institute of Diabetes and Adipositas, Helmholtz Zentrum München, München-Neuherberg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Lutter
authors.affiliation: Institute of Computational Biology, Helmholtz Zentrum München, München-Neuherberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Theis
authors.affiliation: Institute of Structural Biology, Helmholtz Zentrum München, München-Neuherberg, Germany.|Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, 85747 Garching, Germany.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Messias
authors.affiliation: Institute of Structural Biology, Helmholtz Zentrum München, München-Neuherberg, Germany.
authors.forename: Arie
authors.initials: A
authors.lastname: Geerlof
authors.affiliation: Institute of Structural Biology, Helmholtz Zentrum München, München-Neuherberg, Germany.|Center for Integrated Protein Science Munich at Biomolecular NMR Spectroscopy, Department Chemie, Technische Universität München, 85747 Garching, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Sattler
authors.affiliation: Institute of Molecular Immunology, Helmholtz Zentrum München, München-Neuherberg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: Department of Protein Science, Helmholtz Zentrum München, München-Neuherberg, Germany.|Centre of Ophthalmology, Institute for Ophthalmology Research, University of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Boldt
authors.affiliation: Department of Protein Science, Helmholtz Zentrum München, München-Neuherberg, Germany.|Centre of Ophthalmology, Institute for Ophthalmology Research, University of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.affiliation: Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, München-Neuherberg, Germany.|Institute of Stem Cell Research, Helmholtz Zentrum München, München-Neuherberg, Germany.|German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lickert
mesh_terms: D000818:Animals; D002460:Cell Line; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D021381:Protein Transport / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000072086:Smoothened Receptor
chemical_list: C485065:Gprasp2 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; C551745:pitchfork protein, mouse