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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 ?-ketoglutarate (?-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.

SUBMITTER: Cherif H

PROVIDER: S-EPMC5976209 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Cherif Hosni H Duhamel François F Cécyre Bruno B Bouchard Alex A Quintal Ariane A Chemtob Sylvain S Bouchard Jean-François JF

PLoS biology 20180517 5

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 developme ...[more]

PMID: 29771909

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

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

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