Retinal Proteomics of a Mouse Model of Dystroglycanopathies Reveals Molecular Alterations in Photoreceptors
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http://hdl.handle.net/10045/115287
Títol: | Retinal Proteomics of a Mouse Model of Dystroglycanopathies Reveals Molecular Alterations in Photoreceptors |
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Autors: | Uribe, Mary Luz | Martín-Nieto, José | Quereda, Cristina | Rubio-Fernández, Marcos | Cruces, Jesús | Janssen, George M.C. | de Ru, Arnoud H. | van Veelen, Peter A. | Hensbergen, Paul J. |
Grups d'investigació o GITE: | Genética Humana y de Mamíferos (GHM) |
Centre, Departament o Servei: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología | Universidad de Alicante. Instituto Multidisciplinar para el Estudio del Medio "Ramón Margalef" |
Paraules clau: | Mass spectrometry | Retina | POMT1 | Outer segments | KIAA1549 | MDDG |
Àrees de coneixement: | Genética |
Data de publicació: | 23-de maig-2021 |
Editor: | American Chemical Society |
Citació bibliogràfica: | Journal of Proteome Research. 2021, 20(6): 3268-3277. https://doi.org/10.1021/acs.jproteome.1c00126 |
Resum: | Mutations in the POMT1 gene, encoding a protein O-mannosyltransferase essential for α-dystroglycan (α-DG) glycosylation, are frequently observed in a group of rare congenital muscular dystrophies, collectively known as dystroglycanopathies. However, it is hitherto unclear whether the effects seen in affected patients can be fully ascribed to α-DG hypoglycosylation. To study this, here we used comparative mass spectrometry-based proteomics and immunofluorescence microscopy and investigated the changes in the retina of mice in which Pomt1 is specifically knocked out in photoreceptor cells. Our results demonstrate significant proteomic changes and associated structural alteration in photoreceptor cells of Pomt1 cKO mice. In addition to the effects related to impaired α-DG O-mannosylation, we observed morphological alterations in the outer segment that are associated with dysregulation of a relatively understudied POMT1 substrate (KIAA1549), BBSome proteins, and retinal stress markers. In conclusion, our study provides new hypotheses to explain the phenotypic changes that are observed in the retina of patients with dystroglycanopathies. |
Patrocinadors: | Our studies were supported, in part, by the Institute of Health Carlos III grants PI12/0157 and PI15/073 (to J.C. and J.M.-N.), and by the Comunidad de Madrid (“VISIONANIMAL” Biomedicine project S2010/BMD2439 to J.C.) all of them co-financed by the European Regional Development Fund (ERDF/FEDER). Additional research funding was provided by the Universidad de Alicante through grants for use of technical/research facilities (UAUSTI19-17 to J.M.-N.), scientific productivity (VIGROB-237 to J.M.-N.), and a short stay abroad (UAEEBB2015FPU-14 to M.L.U.). |
URI: | http://hdl.handle.net/10045/115287 |
ISSN: | 1535-3893 (Print) | 1535-3907 (Online) |
DOI: | 10.1021/acs.jproteome.1c00126 |
Idioma: | eng |
Tipus: | info:eu-repo/semantics/article |
Drets: | © 2021 The Authors. Published by American Chemical Society. Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0) |
Revisió científica: | si |
Versió de l'editor: | https://doi.org/10.1021/acs.jproteome.1c00126 |
Apareix a la col·lecció: | INV - GHM - Artículos de Revistas |
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Uribe_etal_2021_JProteomeRes.pdf | 4,9 MB | Adobe PDF | Obrir Vista prèvia | |
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