AI Article Synopsis
- - RdCVF is a protective protein secreted by rod photoreceptors that helps prevent cone cell degeneration, which is crucial in retinitis pigmentosa (RP) leading to blindness.
- - The study found that RdCVF interacts with Basigin-1, which in turn facilitates glucose entry into cone cells through the GLUT1 transporter, enhancing their survival through aerobic glycolysis.
- - A specific mutation in RdCVF prevents it from binding to Basigin-1, disrupting glucose uptake and contributing to cone cell death in RP, highlighting a novel way to protect nerve cells by boosting glucose metabolism.
Article Abstract
Rod-derived cone viability factor (RdCVF) is an inactive thioredoxin secreted by rod photoreceptors that protects cones from degeneration. Because the secondary loss of cones in retinitis pigmentosa (RP) leads to blindness, the administration of RdCVF is a promising therapy for this untreatable neurodegenerative disease. Here, we investigated the mechanism underlying the protective role of RdCVF in RP. We show that RdCVF acts through binding to Basigin-1 (BSG1), a transmembrane protein expressed specifically by photoreceptors. BSG1 binds to the glucose transporter GLUT1, resulting in increased glucose entry into cones. Increased glucose promotes cone survival by stimulation of aerobic glycolysis. Moreover, a missense mutation of RdCVF results in its inability to bind to BSG1, stimulate glucose uptake, and prevent secondary cone death in a model of RP. Our data uncover an entirely novel mechanism of neuroprotection through the stimulation of glucose metabolism.
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| http://dx.doi.org/10.1016/j.cell.2015.03.023 | DOI Listing |
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