The Intracellular Loop 2 F328S Frizzled-4 Mutation Implicated in Familial Exudative Vitreoretinopathy Impairs Dishevelled Recruitment
| Autor: | Shujuan Gao, Milly S. Pau, Alexander C. Bertalovitz, Hsien-yu Wang, Craig C. Malbon |
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| Rok vydání: | 2016 |
| Předmět: |
chemistry.chemical_classification
Frizzled Angiogenesis Mutant Wnt signaling pathway Cell Biology Biology medicine.disease Norrin Biochemistry Dishevelled Frizzled-4 Wnt chemistry FEVR Cancer research Familial exudative vitreoretinopathy medicine Receptor Molecular Biology Intracellular Research Article |
| Zdroj: | Journal of Molecular Signaling |
| ISSN: | 1750-2187 |
| Popis: | Familial exudative vitreoretinopathy (FEVR) is a disease state characterized by aberrant retinal angiogenesis. Norrin-induced activation of Frizzled-4 (Fz4) has a major role in regulating beta-catenin levels in the eye that, in turn, modulate the blood retina barrier (BRB). Here we gain insight on the basis of the pathology of a FEVR implicated F328S Fz4 mutant by study. The receptor exhibits a substantially reduced ability to activate Lef/Tcf-dependent transcription. This impaired activation correlates with a decreased ability to stabilize and recruit Dishevelled-2 (Dvl2) to the cell surface. Aromaticity at position 328 of the intracellular loop 2 (iloop2) is revealed similarly as a prerequisite for Dvl2 recruitment to the Fz4. This aromaticity at 328 enables normal Norrin-induced canonical activation. The corresponding position in iloop2 of other Frizzleds likely functions in Dvl recruitment. |
| Databáze: | OpenAIRE |
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