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EPHA2 mutations contribute to congenital cataract through diverse mechanisms
Citation
Dave, A and Martin, S and Kumar, R and Craig, JE and Burdon, KP and Sharma, S, EPHA2 mutations contribute to congenital cataract through diverse mechanisms, Molecular Vision, 22 pp. 18-30. ISSN 1090-0535 (2016) [Refereed Article]
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Copyright Statement
© 2016 Molecular Vision Licensed under Creative Commons Attribution-NonCommercial-NoDerivs License 3.0 Unported (CC BY-NC-ND 3.0) http://creativecommons.org/licenses/by-nc-nd/3.0/
Official URL: http://www.molvis.org/molvis/v22/18/
Abstract
Methods: The effect of five disease-causing mutations, p.P584L (c.1751C>T), p.T940I (c.2819C>T), p.D942fsXC71 (c.2826–9G>A), p.A959T (c.2875G>A), and p.V972GfsX39 (c.2915_2916delTG), on localization of the protein was examined in two in vitro epithelial cell culture systems: Madin-Darby Canine Kidney (MDCK) and human colorectal adenocarcinoma (Caco-2) epithelial cells. Myc-tagged mutant constructs were generated by polymerase chain reaction (PCR)-based mutagenesis. The Myc-tagged wild-type construct was used as a control. The Myc-tagged wild-type and mutant proteins were ectopically expressed and detected by immunofluorescence labeling. Results: Two of the mutations, p.T940I and p.D942fsXC71, located within the cytoplasmic sterile-α-motif (SAM) domain of EPHA2, led to mis-localization of the protein to the perinuclear space and co-localization with the cis-golgi apparatus, indicating sub-organellar/cellular retention of the mutant proteins. The mutant proteins carrying the remaining three mutations, similar to the wild-type EPHA2, localized to the cell membrane.
Conclusions: Mis-localization of two of the mutant proteins in epithelial cells suggests that some disease-causing mutations in EPHA2 likely affect lens epithelial cell homeostasis and contribute to cataract. This study suggests that mutations in EPHA2 contribute to congenital cataract through diverse mechanisms.
Item Details
Item Type: | Refereed Article |
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Keywords: | cataract, disease mechanisms, molecular |
Research Division: | Biomedical and Clinical Sciences |
Research Group: | Ophthalmology and optometry |
Research Field: | Ophthalmology |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Burdon, KP (Professor Kathryn Burdon) |
ID Code: | 105972 |
Year Published: | 2016 |
Web of Science® Times Cited: | 16 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2016-01-21 |
Last Modified: | 2017-11-06 |
Downloads: | 107 View Download Statistics |
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