Usher syndrome type 1–associated cadherins shape the photoreceptor outer segment

Autor: Amrit Estivalet, Asadollah Aghaie, Aziz El-Amraoui, Cataldo Schietroma, Karine Parain, José-Alain Sahel, Muriel Perron, Christine Petit, Jacques Boutet de Monvel, Serge Picaud
Přispěvatelé: Syndrome de Usher et autres atteintes rétino-cochléaires, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et Physiologie de l'Audition, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ED 515 - Complexité du vivant, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Collège de France (CdF (institution)), This work was supported by the FAUN Stiftung (Suchert Foundation), LHW-Stiftung, Retina France, the European Research Council advanced grant 'Hair bundle' (ERC-2011-AdG 294570), the European Union Seventh Framework Program, under grant agreement HEALTH-F2-2010-242013 (TREATRUSH), the French Agence Nationale pour la Recherche as part of the second Investissements d’Avenir program (light4deaf, ANR-15-RHUS-0001), and the LabEx Lifesenses (ANR-10-LABX-65)., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), European Project: 294570,EC:FP7:ERC,ERC-2011-ADG_20110310,HAIRBUNDLE(2012), European Project: 242013,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,TREATRUSH(2010), Oficjalska, Danuta, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Assembling the puzzle of the operating auditory hair bundle - HAIRBUNDLE - - EC:FP7:ERC2012-12-01 - 2017-11-30 - 294570 - VALID, Fighting blindness of Usher syndrome: diagnosis, pathogenesis and retinal treatment (TreatRetUsher) - TREATRUSH - - EC:FP7:HEALTH2010-02-01 - 2014-01-31 - 242013 - VALID, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Chaire Génétique et physiologie cellulaire
Rok vydání: 2017
Předmět:
0301 basic medicine
genetic structures
Xenopus
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Xenopus Proteins
Article
03 medical and health sciences
0302 clinical medicine
CDH23
[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
otorhinolaryngologic diseases
medicine
Animals
Research Articles
Actin
Retina
Gene knockdown
biology
Cadherin
Usher Syndrome Type 1
Gene Expression Regulation
Developmental
Cell Biology
Anatomy
Cadherins
Retinal Photoreceptor Cell Outer Segment
Rod Cell Outer Segment
biology.organism_classification
Photoreceptor outer segment
eye diseases
Cell biology
Actin Cytoskeleton
030104 developmental biology
medicine.anatomical_structure
Gene Knockdown Techniques
Larva
Retinal Cone Photoreceptor Cells
sense organs
Usher Syndromes
030217 neurology & neurosurgery
Zdroj: The Journal of Cell Biology
Journal of Cell Biology
Journal of Cell Biology, 2017, 216 (6), pp.1849-1864. ⟨10.1083/jcb.201612030⟩
Journal of Cell Biology, Rockefeller University Press, 2017, 216 (6), pp.1849-1864. ⟨10.1083/jcb.201612030⟩
ISSN: 1540-8140
0021-9525
Popis: Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but USH1 protein function in the retina is unclear. Schietroma et al. use Xenopus to model the deficiency in two USH1 proteins—protocadherin-15 and cadherin-23—and identify crucial roles for these molecules in shaping the photoreceptor outer segment.
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal.
Databáze: OpenAIRE
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