Cargando…
Retinal Proteomics of a Mouse Model of Dystroglycanopathies Reveals Molecular Alterations in Photoreceptors
[Image: see text] 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 t...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2021
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280732/ https://www.ncbi.nlm.nih.gov/pubmed/34027671 http://dx.doi.org/10.1021/acs.jproteome.1c00126 |
_version_ | 1783722700498272256 |
---|---|
author | 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. |
author_facet | 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. |
author_sort | Uribe, Mary Luz |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-8280732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-82807322021-07-16 Retinal Proteomics of a Mouse Model of Dystroglycanopathies Reveals Molecular Alterations in Photoreceptors 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. J Proteome Res [Image: see text] 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. American Chemical Society 2021-05-24 2021-06-04 /pmc/articles/PMC8280732/ /pubmed/34027671 http://dx.doi.org/10.1021/acs.jproteome.1c00126 Text en © 2021 The Authors. Published by American Chemical Society Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | 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. Retinal Proteomics of a Mouse Model of Dystroglycanopathies Reveals Molecular Alterations in Photoreceptors |
title | Retinal Proteomics
of a Mouse Model of Dystroglycanopathies
Reveals Molecular Alterations in Photoreceptors |
title_full | Retinal Proteomics
of a Mouse Model of Dystroglycanopathies
Reveals Molecular Alterations in Photoreceptors |
title_fullStr | Retinal Proteomics
of a Mouse Model of Dystroglycanopathies
Reveals Molecular Alterations in Photoreceptors |
title_full_unstemmed | Retinal Proteomics
of a Mouse Model of Dystroglycanopathies
Reveals Molecular Alterations in Photoreceptors |
title_short | Retinal Proteomics
of a Mouse Model of Dystroglycanopathies
Reveals Molecular Alterations in Photoreceptors |
title_sort | retinal proteomics
of a mouse model of dystroglycanopathies
reveals molecular alterations in photoreceptors |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280732/ https://www.ncbi.nlm.nih.gov/pubmed/34027671 http://dx.doi.org/10.1021/acs.jproteome.1c00126 |
work_keys_str_mv | AT uribemaryluz retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors AT martinnietojose retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors AT queredacristina retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors AT rubiofernandezmarcos retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors AT crucesjesus retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors AT janssengeorgemc retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors AT deruarnoudh retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors AT vanveelenpetera retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors AT hensbergenpaulj retinalproteomicsofamousemodelofdystroglycanopathiesrevealsmolecularalterationsinphotoreceptors |