Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice.

Détails

Ressource 1Télécharger: BIB_790E836A2CAF.P001.pdf (981.66 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_790E836A2CAF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice.
Périodique
Journal of Clinical Investigation
Auteur(s)
Yang Z., Chen Y., Lillo C., Chien J., Yu Z., Michaelides M., Klein M., Howes K.A., Li Y., Kaminoh Y., Chen H., Zhao C., Chen Y., Al-Sheikh Y.T., Karan G., Corbeil D., Escher P., Kamaya S., Li C., Johnson S., Frederick J.M., Zhao Y., Wang C., Cameron D.J., Huttner W.B., Schorderet D.F., Munier F.L., Moore A.T., Birch D.G., Baehr W., Hunt D.M., Williams D.S., Zhang K.
ISSN
0021-9738
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
118
Numéro
8
Pages
2908-29016
Langue
anglais
Résumé
Familial macular degeneration is a clinically and genetically heterogeneous group of disorders characterized by progressive central vision loss. Here we show that an R373C missense mutation in the prominin 1 gene (PROM1) causes 3 forms of autosomal-dominant macular degeneration. In transgenic mice expressing R373C mutant human PROM1, both mutant and endogenous PROM1 were found throughout the layers of the photoreceptors, rather than at the base of the photoreceptor outer segments, where PROM1 is normally localized. Moreover, the outer segment disk membranes were greatly overgrown and misoriented, indicating defective disk morphogenesis. Immunoprecipitation studies showed that PROM1 interacted with protocadherin 21 (PCDH21), a photoreceptor-specific cadherin, and with actin filaments, both of which play critical roles in disk membrane morphogenesis. Collectively, our results identify what we believe to be a novel complex involved in photoreceptor disk morphogenesis and indicate a possible role for PROM1 and PCDH21 in macular degeneration.
Mots-clé
Animals, Antigens, CD/genetics, Antigens, CD/metabolism, Cadherins/metabolism, Electroretinography, Glycoproteins/genetics, Glycoproteins/metabolism, Humans, Macular Degeneration/genetics, Macular Degeneration/physiopathology, Mice, Mice, Transgenic, Microfilaments/metabolism, Morphogenesis, Mutation, Missense, Nerve Tissue Proteins/metabolism, Peptides/genetics, Peptides/metabolism, Photoreceptor Cells, Vertebrate/metabolism, Photoreceptor Cells, Vertebrate/ultrastructure
Pubmed
Web of science
Open Access
Oui
Création de la notice
05/10/2009 15:49
Dernière modification de la notice
20/08/2019 14:35
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