TY - JOUR
T1 - Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis
AU - Aït-Ali, Najate
AU - Fridlich, Ram
AU - Millet-Puel, Géraldine
AU - Clérin, Emmanuelle
AU - Delalande, François
AU - Jaillard, Céline
AU - Blond, Frédéric
AU - Perrocheau, Ludivine
AU - Reichman, Sacha
AU - Byrne, Leah C.
AU - Olivier-Bandini, Anne
AU - Bellalou, Jacques
AU - Moyse, Emmanuel
AU - Bouillaud, Frédéric
AU - Nicol, Xavier
AU - Dalkara, Deniz
AU - Van Dorsselaer, Alain
AU - Sahel, José Alain
AU - Léveillard, Thierry
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/7
Y1 - 2015/5/7
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84928921985
U2 - 10.1016/j.cell.2015.03.023
DO - 10.1016/j.cell.2015.03.023
M3 - Article
C2 - 25957687
AN - SCOPUS:84928921985
SN - 0092-8674
VL - 161
SP - 817
EP - 832
JO - Cell
JF - Cell
IS - 4
ER -