PUBLICATION
Eyes shut homolog (EYS) interacts with matriglycan of O-mannosyl glycans whose deficiency results in EYS mislocalization and degeneration of photoreceptors
- Authors
- Liu, Y., Yu, M., Shang, X., Nguyen, M.H.H., Balakrishnan, S., Sager, R., Hu, H.
- ID
- ZDB-PUB-200510-13
- Date
- 2020
- Source
- Scientific Reports 10: 7795 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Mice
- Mutation
- Eye Proteins/genetics*
- Eye Proteins/metabolism*
- Secretory Vesicles/metabolism
- Gene Deletion*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- Protein Transport
- Amino Acid Sequence
- Zebrafish/genetics
- Zebrafish/metabolism
- Synaptotagmin I/metabolism
- Animals
- Glycosylation
- Photoreceptor Cells/metabolism*
- Polysaccharides/metabolism*
- Retina/metabolism
- Retina/pathology
- PubMed
- 32385361 Full text @ Sci. Rep.
Citation
Liu, Y., Yu, M., Shang, X., Nguyen, M.H.H., Balakrishnan, S., Sager, R., Hu, H. (2020) Eyes shut homolog (EYS) interacts with matriglycan of O-mannosyl glycans whose deficiency results in EYS mislocalization and degeneration of photoreceptors. Scientific Reports. 10:7795.
Abstract
Mutations in eyes shut homolog (EYS), a secreted extracellular matrix protein containing multiple laminin globular (LG) domains, and in protein O-mannose β1, 2-N-acetylglucosaminyl transferase 1 (POMGnT1), an enzyme involved in O-mannosyl glycosylation, cause retinitis pigmentosa (RP), RP25 and RP76, respectively. How EYS and POMGnT1 regulate photoreceptor survival is poorly understood. Since some LG domain-containing proteins function by binding to the matriglycan moiety of O-mannosyl glycans, we hypothesized that EYS interacted with matriglycans as well. To test this hypothesis, we performed EYS Far-Western blotting assay and generated pomgnt1 mutant zebrafish. The results showed that EYS bound to matriglycans. Pomgnt1 mutation in zebrafish resulted in a loss of matriglycan, retention of synaptotagmin-1-positive EYS secretory vesicles within the outer nuclear layer, and diminished EYS protein near the connecting cilia. Photoreceptor density in 2-month old pomgnt1 mutant retina was similar to the wild-type animals but was significantly reduced at 6-months. These results indicate that EYS protein localization to the connecting cilia requires interaction with the matriglycan and that O-mannosyl glycosylation is required for photoreceptor survival in zebrafish. This study identified a novel interaction between EYS and matriglycan demonstrating that RP25 and RP76 are mechanistically linked in that O-mannosyl glycosylation controls targeting of EYS protein.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping