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Receptors of intermediates of carbohydrate metabolism, GPR91 and GPR99, mediate axon growth

Authors: Hosni Cherif; François Duhamel; Bruno Cécyre; Alex Bouchard; Ariane Quintal; Sylvain Chemtob; Jean-François Bouchard;

Receptors of intermediates of carbohydrate metabolism, GPR91 and GPR99, mediate axon growth

Abstract

During the development of the visual system, high levels of energy are expended propelling axons from the retina to the brain. However, the role of intermediates of carbohydrate metabolism in the development of the visual system has been overlooked. Here, we report that the carbohydrate metabolites succinate and α-ketoglutarate (α-KG) and their respective receptor-GPR91 and GPR99-are involved in modulating retinal ganglion cell (RGC) projections toward the thalamus during visual system development. Using ex vivo and in vivo approaches, combined with pharmacological and genetic analyses, we revealed that GPR91 and GPR99 are expressed on axons of developing RGCs and have complementary roles during RGC axon growth in an extracellular signal-regulated kinases 1 and 2 (ERK1/2)-dependent manner. However, they have no effects on axon guidance. These findings suggest an important role for these receptors during the establishment of the visual system and provide a foundational link between carbohydrate metabolism and axon growth.

Keywords

Mice, Knockout, Retinal Ganglion Cells, QH301-705.5, MAP Kinase Signaling System, Receptors, Purinergic P2, Neuronal Outgrowth, Succinic Acid, Retina, Receptors, G-Protein-Coupled, Mice, Short Reports, Animals, Carbohydrate Metabolism, Ketoglutaric Acids, Biology (General)

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    22
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
22
Top 10%
Top 10%
Top 10%
Green
gold