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

PLoS Biology
Hosni CherifJean-François Bouchard

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.

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Citations

Oct 31, 2020·Journal of Receptor and Signal Transduction Research·Loranda Calderón-ZamoraSantiago Villafaña
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Xiayin ZhangHaotian Lin
Jul 3, 2021·Cells·Samuel LarocheJean-François Bouchard

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Methods Mentioned

BETA
PCR
genetic modifications

Software Mentioned

Deltagen
MATLAB
LCS
Pro Plus
Image
Systat

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