title: Localization of Usher 1 proteins to the photoreceptor calyceal processes, which are absent from mice.
abstract: The mechanisms underlying retinal dystrophy in Usher syndrome type I (USH1) remain unknown because mutant mice lacking any of the USH1 proteins-myosin VIIa, harmonin, cadherin-23, protocadherin-15, sans-do not display retinal degeneration. We found here that, in macaque photoreceptor cells, all USH1 proteins colocalized at membrane interfaces (i) between the inner and outer segments in rods and (ii) between the microvillus-like calyceal processes and the outer segment basolateral region in rods and cones. This pattern, conserved in humans and frogs, was mediated by the formation of an USH1 protein network, which was associated with the calyceal processes from the early embryonic stages of outer segment growth onwards. By contrast, mouse photoreceptors lacked calyceal processes and had no USH1 proteins at the inner-outer segment interface. We suggest that USH1 proteins form an adhesion belt around the basolateral region of the photoreceptor outer segment in humans, and that defects in this structure cause the retinal degeneration in USH1 patients.
authors.affiliation: Institut de la vision, Syndrome de Usher et autres Atteintes Rétino-Cochléaires, 75012 Paris, France.
authors.forename: Iman
authors.initials: I
authors.lastname: Sahly
authors.forename: Eric
authors.initials: E
authors.lastname: Dufour
authors.forename: Cataldo
authors.initials: C
authors.lastname: Schietroma
authors.forename: Vincent
authors.initials: V
authors.lastname: Michel
authors.forename: Amel
authors.initials: A
authors.lastname: Bahloul
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perfettini
authors.forename: Elise
authors.initials: E
authors.lastname: Pepermans
authors.forename: Amrit
authors.initials: A
authors.lastname: Estivalet
authors.forename: Diane
authors.initials: D
authors.lastname: Carette
authors.forename: Asadollah
authors.initials: A
authors.lastname: Aghaie
authors.forename: Inga
authors.initials: I
authors.lastname: Ebermann
authors.forename: Andrea
authors.initials: A
authors.lastname: Lelli
authors.forename: Maria
authors.initials: M
authors.lastname: Iribarne
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
authors.forename: Dominique
authors.initials: D
authors.lastname: Weil
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.forename: Aziz
authors.initials: A
authors.lastname: El-Amraoui
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: D000818:Animals; D001001:Anura; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D008252:Macaca fascicularis; D051379:Mice; D000081412:Myosin VIIa; D009218:Myosins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism* / Q000648:ultrastructure*; D011498:Protein Precursors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000648:ultrastructure; D058499:Retinal Dystrophies / Q000473:pathology; D013552:Swine; D052245:Usher Syndromes / Q000378:metabolism* / Q000473:pathology
chemical_list: C418976:CDHR15 protein, mouse; D000070585:Cadherin Related Proteins; D015820:Cadherins; D002352:Carrier Proteins; C499091:Cdh23 protein, mouse; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C000631455:MYO7A protein, human; C000631456:Myo7a protein, mouse; D000081412:Myosin VIIa; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; C477451:Sans protein, mouse; C492262:Ush1c protein, mouse; D009218:Myosins