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J Cell Biol. 2017 Jun 5;216(6):1849-1864. doi: 10.1083/jcb.201612030. Epub 2017 May 11.

Usher syndrome type 1-associated cadherins shape the photoreceptor outer segment.

Author information

1
Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France.
2
Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-UMRS 1120, France.
3
Sorbonne Universités, UPMC University Paris, Complexité du Vivant, 75005 Paris, France.
4
Syndrome de Usher et Autres Atteintes Rétino-Cochléaires, Institut de la Vision, 75012 Paris, France.
5
Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris Sud, Université Paris-Saclay, 91405 Orsay, France.
6
Retinal information processing - Pharmacology and Pathology, Institut de la Vision, 75012 Paris, France.
7
Centre d'Etude et de Recherche Thérapeutique en Ophtalmologie, Retina France, 94405 Orsay, France.
8
Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France aziz.el-amraoui@pasteur.fr christine.petit@pasteur.fr.
9
Collège de France, 75005 Paris, France.

Abstract

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.

PMID:
28495838
PMCID:
PMC5461027
DOI:
10.1083/jcb.201612030
[Indexed for MEDLINE]
Free PMC Article

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