TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome
Autor: | Michelle Peckham, Karl Gaff, Alistair Curd, Martijn A. Huynen, Oliver E. Blacque, Ka Man Wu, Colin A. Johnson, Laurence Faivre, Rachel H. Giles, Diane Doummar, Nils J. Lambacher, Tania Attié-Bitach, Lydie Burglen, Gisela G. Slaats, Christel Thauvin-Robinet, Ange-Line Bruel, Gavin J. McManus, Katarzyna Szymanska, Sophie Saunier, Julie Kennedy, Teunis J. P. van Dam, Robin van der Lee, Jean-Baptiste Rivière, Stefanie Kuhns |
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Přispěvatelé: | School of Biology & Environmental Science and Conway Institute of Biomolecular & Biomedical Research, University College Dublin, University College Dublin [Dublin] ( UCD ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Radboud University Medical Center [Nijmegen], Leeds Institute of Biomedical & Clinical Sciences ( LIBACS ), University of Leeds, University Medical Center [Utrecht], Service de neuropédiatrie et pathologie du développement, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Service de Génétique et d'Embryologie Médicale, Service de neuropédiatrie [Trousseau], CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Proteome Research Centre, UCD Conway Institute for Biomolecular and Biomedical Research, European Community's Seventh Framework Programme 241955 Science Foundation Ireland 11/PI/1037 Dutch Kidney Foundation CP11.18 GIS-Institut des Maladies Rares French Fondation for Rare Disease Virgo consortium FE50908 Netherlands Genomics Initiative 050-060-452 French Ministry of Health (PHRC national) 2010-A01014-35 Fondation pour la Recherche Medicale DEQ20130326532 Regional Council of Burgundy Sir Jules Thorn Award for Biomedical Research JTA/09 UK Medical Research Council MR/K011154/1 MR1K015613/1 Lung GO Sequencing Project HL-102923 WHI Sequencing Project HL-102924 Broad GO Sequencing Project HL-102925 Seattle GO Sequencing Project HL-102926 Heart GO Sequencing Project HL-103010 University of Leeds, University College Dublin [Dublin] (UCD), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Leeds Institute of Biomedical & Clinical Sciences (LIBACS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Biology Research Support nephrocystins Joubert syndrome Retina Article 03 medical and health sciences Nephronophthisis Ciliogenesis [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology Cerebellum evolution medicine Journal Article Animals Humans Abnormalities Multiple Cilia Eye Abnormalities Caenorhabditis elegans Caenorhabditis elegans Proteins Non-U.S. Gov't membrane Cilium c. elegans Research Support Non-U.S. Gov't Ciliary transition zone Membrane Proteins Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] Cell Biology Kidney Diseases Cystic medicine.disease mutations Cell biology Ciliopathy caenorhabditis-elegans 030104 developmental biology Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] Membrane protein transport Ciliary base [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology complex ciliogenesis primary cilium |
Zdroj: | Nature Cell Biology, 18, 122-31 Nature Cell Biology Nature Cell Biology, Nature Publishing Group, 2016, 18 (1), pp.122-131. 〈10.1038/ncb3273〉 Nature Cell Biology, Nature Publishing Group, 2016, 18 (1), pp.122-131. ⟨10.1038/ncb3273⟩ Nature Cell Biology, 18, 1, pp. 122-31 |
ISSN: | 1465-7392 1476-4679 |
Popis: | Item does not contain fulltext The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome (JBTS). However, the molecular composition and mechanisms underpinning TZ organization and barrier regulation are poorly understood. To uncover candidate TZ genes, we employed bioinformatics (coexpression and co-evolution) and identified TMEM107 as a TZ protein mutated in oral-facial-digital syndrome and JBTS patients. Mechanistic studies in Caenorhabditis elegans showed that TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors. Furthermore, nematode TMEM-107 occupies an intermediate layer of the TZ-localized MKS module by organizing recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20) and JBTS-14 (TMEM237). Finally, MKS module membrane proteins are immobile and super-resolution microscopy in worms and mammalian cells reveals periodic localizations within the TZ. This work expands the MKS module of ciliopathy-causing TZ proteins associated with diffusion barrier formation and provides insight into TZ subdomain architecture. |
Databáze: | OpenAIRE |
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