PUBLICATION
KPNA4 is involved in cataract formation via the nuclear import of p53
- Authors
- Ping, X., Cheng, Y., Bao, J., Shi, K., Zou, J., Shentu, X.
- ID
- ZDB-PUB-210407-10
- Date
- 2021
- Source
- Gene 786: 145621 (Journal)
- Registered Authors
- Zou, Jian
- Keywords
- KPNA4, cataract, nuclear transport, p53, zebrafish
- MeSH Terms
-
- Active Transport, Cell Nucleus
- Animals
- Cataract/diagnostic imaging*
- Cataract/genetics
- Cataract/metabolism
- Cell Line
- Cell Nucleus/metabolism
- Cell Survival/drug effects
- Disease Models, Animal
- Epithelial Cells/cytology
- Epithelial Cells/drug effects
- Epithelial Cells/metabolism
- Gene Knockout Techniques
- Humans
- Hydrogen Peroxide/adverse effects
- Lens, Crystalline/cytology
- Lens, Crystalline/drug effects
- Lens, Crystalline/metabolism
- Microscopy, Electron, Transmission
- Tumor Suppressor Protein p53/metabolism*
- Zebrafish
- alpha Karyopherins/genetics*
- alpha Karyopherins/metabolism*
- PubMed
- 33798680 Full text @ Gene
Citation
Ping, X., Cheng, Y., Bao, J., Shi, K., Zou, J., Shentu, X. (2021) KPNA4 is involved in cataract formation via the nuclear import of p53. Gene. 786:145621.
Abstract
KPNA4 (also called importin-α3) belongs to the importin α adaptor proteins family, which orchestrates classical nuclear transport processes, importin-α/importin-β1 pathway, and involves in cellular homeostasis. Disruption of balanced transport pathways may result in ectopic nuclear proteins and eventually cause diseases, mainly under the situation of cellular stress, such as oxidative stress. Little evidence is available on its cellular functions for high specific expression in lens. We firstly studied the role of KPNA4 in cataract formation. Lens defects were observed at an early age in kpna4 gene knockout zebrafish, generated by the CRISPR/Cas9 system. Those phenotype, including cloudy center part of the lens, via bright field microscopy, and the thinning of the LE layer, wider space between the adjacent LE and LF cells, irregular cells morphology and the increased number of holes inside the LE cells, which were detected by transmission electron microscopy, recapitulate the clinical features of cataract patients. As the p53-specific adaptor of the nuclear import, KPNA4 upregulated with the same pattern of p53 in hydrogen peroxide-induced apoptosis in human lens epithelia cells. Furthermore, the loss of Kpna4 resulted in the accumulation of p53 in the center of lens. Taken together, we showed that KPNA4 was involved in the formation of cataract, likely by mediating p53 nuclear transport.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping