Retinal Proteomics of a Mouse Model of Dystroglycanopathies Reveals Molecular Alterations in Photoreceptors.
Mary Luz UribeJosé Martín-NietoCristina QueredaMarcos Rubio-FernándezJesús CrucesGeorge M C JanssenArnoud H de RuPeter A van VeelenPaul J HensbergenPublished in: Journal of proteome research (2021)
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.
Keyphrases
- mass spectrometry
- induced apoptosis
- diabetic retinopathy
- optical coherence tomography
- mouse model
- label free
- cell cycle arrest
- optic nerve
- high resolution
- ejection fraction
- liquid chromatography
- signaling pathway
- prognostic factors
- single molecule
- cell proliferation
- high speed
- adipose tissue
- high throughput
- gas chromatography
- high performance liquid chromatography
- patient reported outcomes
- resistance training
- drug induced
- simultaneous determination
- atomic force microscopy