Rod-Derived Cone Viability Factor Promotes Cone Survival by Stimulating Aerobic Glycolysis

被引：332

作者：

Ait-Ali, Najate ^{[1
,2
,3
]}

Fridlich, Ram ^{[1
,2
,3
]}

Millet-Puel, Geraldine ^{[1
,2
,3
]}

Clerin, Emmanuelle ^{[1
,2
,3
]}

Delalande, Francois ^{[4
,5
]}

Jaillard, Celine ^{[1
,2
,3
]}

Blond, Frederic ^{[1
,2
,3
]}

Perrocheau, Ludivine ^{[1
,2
,3
]}

Reichman, Sacha ^{[1
,2
,3
]}

Byrne, Leah C. ^{[6
]}

Olivier-Bandini, Anne ^{[7
]}

Bellalou, Jacques ^{[8
]}

Moyse, Emmanuel ^{[9
]}

Bouillaud, Frederic ^{[10
,11
,12
]}

Nicol, Xavier ^{[1
,2
,3
]}

Dalkara, Deniz ^{[1
,2
,3
]}

van Dorsselaer, Alain ^{[4
,5
]}

Sahel, Jose-Alain ^{[1
,2
,3
]}

Leveillard, Thierry ^{[1
,2
,3
]}

机构：

[1] INSERM, U968, F-75012 Paris, France

[2] Univ Paris 06, Sorbonne Univ, UMR S 968, Inst Vis, F-75012 Paris, France

[3] CNRS, UMR 7210, F-75012 Paris, France

[4] Univ Strasbourg, IPHC, BioOrgan Mass Spectrometry Lab LSMBO, F-67087 Strasbourg, France

[5] CNRS, IPHC, UMR7178, F-67087 Strasbourg, France

[6] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA

[7] Sanofi R&D, F-91385 Chilly Mazarin, France

[8] Inst Pasteur, Platform Prod Recombinant Prot & Antibodies 5, F-75724 Paris 15, France

[9] Univ Francois Rabelais Tours, Ctr INRA Tours, Unite Physiol Reprod & Comportements PRC, UMR INRA 85, F-37380 Nouzilly, France

[10] INSERM, U1016, Inst Cochin, F-75014 Paris, France

[11] CNRS, UMR8104, F-75014 Paris, France

[12] Univ Paris 05, Sorbonne Paris Cite, F-75014 Paris, France

来源：

CELL | 2015年 / 161卷 / 04期

关键词：

THIOREDOXIN-LIKE PROTEIN; PYRUVATE-KINASE; RDCVF; EXPRESSION; CD147; PHOTORECEPTORS; DYSFUNCTION; SECRETION; RESCUE; MODEL;

D O I：

10.1016/j.cell.2015.03.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：817 / 832

页数：16

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