July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 governs the metabolic flux between rod and cone photoreceptors
Author Affiliations & Notes
  • Géraldine Millet Puel
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Marie Cordonnier
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Alexandra Saint-charles
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Emmanuelle Clerin
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Frédéric Blond
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Seiki Achiedo
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Najate Ait-Ali
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Orna Corchia
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Laurence Klipfel
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Ying Yang
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Raju V S Rajala
    Department of Ophthalmology and Physiology, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma, United States
  • Erika Tatiana Camacho
    School of Mathematical & Natural Sciences, Arizona State University, Glendale, Arizona, United States
  • Thierry D Leveillard
    Department of Genetics, Sorbonne Université, INSERM, CNRS, Institut de la Vision, Paris, Paris, France
  • Footnotes
    Commercial Relationships   Géraldine Puel, Patent Number :16306592.3-1466 (P); Marie Cordonnier, None; Alexandra Saint-charles, None; Emmanuelle Clerin, None; Frédéric Blond, None; Seiki Achiedo, None; Najate Ait-Ali, None; Orna Corchia, None; Laurence Klipfel, None; Ying Yang, None; Raju Rajala, None; Erika Camacho, None; Thierry Leveillard, Patent Number :16306592.3-1466 (P)
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6404. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Géraldine Millet Puel, Marie Cordonnier, Alexandra Saint-charles, Emmanuelle Clerin, Frédéric Blond, Seiki Achiedo, Najate Ait-Ali, Orna Corchia, Laurence Klipfel, Ying Yang, Raju V S Rajala, Erika Tatiana Camacho, Thierry D Leveillard; 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 governs the metabolic flux between rod and cone photoreceptors. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6404.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : In retinitis pigmentosa (RP) cones degenerate after rods, independently on the mutation in any of the 64 genes known to be associated with the disease. Rod-derived Cone Viability Factor (RdCVF) is secreted by rods and exerts a protective effect on cones by binding to a complex consisting of a cell surface receptor, basigin-1 (BSG1) and the glucose transporter, GLUT1 (SLC2A1). Since both cones and rods, express BSG1, we investigated the directionality of the RdCVF metabolic signaling.

Methods : Transcriptomic analysis, in situ hybridization, Western blotting, immunohistochemistry techniques were used to study the expression profile of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2) in the wild-type and the rd1 mouse (a mouse model of autosomal recessive RP) retina. Primary cone-enriched cultures coupled with electroporation was used to study both promoter and enzymatic activities of PFKFB2 and interpreted the results using a bio-mathematical modeling.

Results : PFKFB2, is a bifunctional enzyme that regulates the flux of glycolysis through the production or destruction of fructose 2,6 bisphosphate (F26BP). F26BP is the major allosteric activator of phosphofructokinase, the rate-limiting enzyme of glycolysis. Our results show that PFKFB2 is expressed specifically in cones in a rod-dependent manner. We found the expression of PFKFB2 mRNA is increased by glucose, and consistent with this observation, the promoter region of PFKFB2 contains a DNA element that responds to glucose. Our results also show a loss of PFKFB2 expression in rd1 mouse cones precedes their death, and ectopic expression of PFKFB2 kinase domain promote cone survival. In wild-type mouse cones, PFKFB2 undergoes serine phosphorylation that regulates kinase activity of the enzyme by inhibiting its intrinsic phosphatase activity. Bio-mathematical modeling shows the directionality of RdCVF flux flows from rod to cone photoreceptors.

Conclusions : Our findings clearly demonstrate that PFKFB2 stimulates aerobic glycolysis in cones, a downstream effector of BSG1/GLUT1 complex activated by rod-secreted RdCVF. Our studies also show the directionally of RdCVF metabolic signaling flows from rod toward cone photoreceptors.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×