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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Functional analysis of disease-associated polymorphism LRP5.Q89R
Weiming Mao1, Robert J Wordinger, Abbot F Clark
1Department of Cell Biology & Anatomy, North Texas Eye Research Institute, University of North Texas Health Science Center, Ft. Worth, TX, USA. Weiming.mao@unthsc.edu
Molecular Vision
|April 30, 2011
Summary
The LRP5.Q89R polymorphism, linked to retinal diseases, does not affect the Wnt signaling pathway. Further research on LRP5 variations is needed to understand their role in disease.
Area of Science:
- Genetics and Molecular Biology
- Ophthalmology
- Cell Signaling
Background:
- The canonical Wingless and Int1 (Wnt) signaling pathway is crucial for numerous biological processes.
- Low density lipoprotein receptor-related protein 5 (LRP5), a Wnt pathway co-receptor, is implicated in retinal disease pathogenesis, including glaucoma.
Purpose of the Study:
- To investigate whether the disease-associated LRP5.Q89R polymorphism directly impacts Wnt signaling activity.
- To assess the effect of LRP5.Q89R on Wnt signaling transduction and its inhibition by Dickkopf-1 (DKK-1).
Main Methods:
- HEK293T and GTM3 cells were transfected with expression vectors for the LRP5.Q89R polymorphism.
- LRP5 expression, interaction with MESD, and membrane localization were analyzed using western immunoblotting and co-immunoprecipitation.
- TCF-reporter luciferase assays were employed to evaluate Wnt signaling activity and DKK-1 inhibition efficacy.
Main Results:
- The LRP5.Q89R polymorphism did not alter LRP5 protein expression or its interaction with the chaperone MESD.
- Cell-based assays demonstrated no significant changes in protein trafficking or Wnt signaling transduction.
- The efficacy of DKK-1-mediated inhibition of Wnt signaling remained unaffected by the LRP5.Q89R polymorphism.
Conclusions:
- The studied LRP5.Q89R polymorphism does not appear to modify the canonical Wnt signaling pathway.
- Further investigation into other LRP5 polymorphisms is warranted to clarify their contributions to associated diseases.
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