PUBLICATION
Deletion of the transmembrane protein Prom1b in zebrafish disrupts outer-segment morphogenesis and causes photoreceptor degeneration
- Authors
- Lu, Z., Hu, X., Reilly, J., Jia, D., Liu, F., Yu, S., Liu, X., Xie, S., Qu, Z., Qin, Y., Huang, Y., Lv, Y., Li, J., Gao, P., Wong, F., Shu, X., Tang, Z., Liu, M.
- ID
- ZDB-PUB-190801-20
- Date
- 2019
- Source
- The Journal of biological chemistry 294(38): 13953-13963 (Journal)
- Registered Authors
- Huang, Yuwen, Hu, Xuebin, Li, Jingzhen, Liu, Fei, Liu, Mugen, Liu, Xiliang, Lu, Zhaojing, Qin, Yayun, Qu, Zhen, Yu, Shanshan
- Keywords
- Danio rerio, development, eye disease, morphogenesis, peripherin 2 (PRPH2), photoreceptor, prominin 1 (PROM1), retinal degeneration, zebrafish
- MeSH Terms
-
- AC133 Antigen/genetics
- AC133 Antigen/metabolism*
- Animals
- Cone-Rod Dystrophies/genetics
- Disease Models, Animal
- HeLa Cells
- Humans
- Macular Degeneration/metabolism
- Membrane Proteins/metabolism
- Morphogenesis
- Mutation
- Peripherins/genetics
- Photoreceptor Cells/metabolism*
- Retina/metabolism
- Retina/physiology
- Retinal Cone Photoreceptor Cells/metabolism
- Retinal Degeneration/genetics
- Retinal Degeneration/physiopathology
- Retinal Rod Photoreceptor Cells/metabolism
- Retinitis Pigmentosa/genetics
- Rod Cell Outer Segment/metabolism*
- Sequence Deletion
- Zebrafish/metabolism
- Zebrafish Proteins/metabolism
- PubMed
- 31362982 Full text @ J. Biol. Chem.
Citation
Lu, Z., Hu, X., Reilly, J., Jia, D., Liu, F., Yu, S., Liu, X., Xie, S., Qu, Z., Qin, Y., Huang, Y., Lv, Y., Li, J., Gao, P., Wong, F., Shu, X., Tang, Z., Liu, M. (2019) Deletion of the transmembrane protein Prom1b in zebrafish disrupts outer-segment morphogenesis and causes photoreceptor degeneration. The Journal of biological chemistry. 294(38):13953-13963.
Abstract
Mutations in human prominin 1 (PROM1), encoding a transmembrane glycoprotein localized mainly to plasma membrane protrusions, have been reported to cause retinitis pigmentosa, macular degeneration and cone-rod dystrophy. Although the structural role of PROM1 in outer-segment (OS) morphogenesis has been demonstrated in Prom1-knockout mouse, the mechanisms underlying these complex disease phenotypes remain unclear. Here we utilized a zebrafish model to further investigate PROM1's role in the retina. The Prom1 orthologs in zebrafish include prom1a and prom1b, and our results showed that prom1b, rather than prom1a, plays an important role in zebrafish photoreceptors. Loss of prom1b disrupted OS morphogenesis, with rods and cones exhibiting differences in impairment: cones degenerated at an early age, whereas rods remained viable, but with an abnormal OS, even at 9 months post-fertilization. Immunofluorescence experiments with WT zebrafish revealed that Prph2, an ortholog of the human transmembrane protein peripherin 2 and also associated with OS formation, is localized to the edge of OS and is more highly expressed in the cone OS than in the rod OS. Moreover, we found that Prom1b deletion causes mislocalization of Prph2 and disrupts its oligomerization. We conclude that the variation in Prph2 levels between cones and rods was one of the reasons for the different PROM1 mutation-induced phenotypes of these retinal structures. These findings expand our understanding of the phenotypes caused by PROM1 mutations and provide critical insights into its function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping