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

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Schietroma, Cataldo | Parain, Karine | Estivalet, Amrit | Aghaie, Asadollah | Boutet de Monvel, Jacques | Picaud, Serge | Sahel, José-Alain | Perron, Muriel | El-Amraoui, Aziz | Petit, Christine

Edité par CCSD ; Rockefeller University Press -

International audience. Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead toretinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which aremicrovilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopustropicalis, 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 photoreceptorfunction 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 ofCdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayedmarkedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their developmentand/or maintenance. We propose that calyceal processes, together with their associated links, control thesizing of rod disks and cone lamellae throughout their daily renewal.

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