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Cell. 2015 May 7;161(4):817-32. doi: 10.1016/j.cell.2015.03.023.

Rod-derived cone viability factor promotes cone survival by stimulating aerobic glycolysis.

Author information

1
INSERM, U968, 75012 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France.
2
BioOrganic Mass Spectrometry Laboratory (LSMBO), IPHC, Université de Strasbourg, 25 rue Becquerel, 67087 Strasbourg, France; IPHC, CNRS, UMR7178, 67087 Strasbourg, France.
3
Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA 94720, USA.
4
Sanofi R&D, 1 Avenue Pierre Brossolette, 91385 Chilly-Mazarin, France.
5
Institut Pasteur, Platform 5 Production of Recombinant Proteins and Antibodies, 75724 Paris Cedex 15, France.
6
Unité de Physiologie de la Reproduction et des Comportements (PRC), UMR-85 INRA, Centre INRA de Tours, Université François Rabelais de Tours, 37380 Nouzilly, France.
7
Inserm, U1016, Institut Cochin, 75014 Paris, France; Cnrs, UMR8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75014 Paris, France.
8
INSERM, U968, 75012 Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France; CNRS, UMR_7210, 75012 Paris, France. Electronic address: thierry.leveillard@inserm.fr.

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.

PMID:
25957687
DOI:
10.1016/j.cell.2015.03.023
[Indexed for MEDLINE]
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