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Title: Synaptic activity-induced glycolysis facilitates membrane lipid provision and neurite outgrowth
Author: Segarra Mondéjar, Marc
Casellas Díaz, Sergi
Ramiro-Pareta, Marina
Mueller-Sanchez, Claudia
Martorell Riera, Alejandro
Hermelo, Ismail
Reina del Pozo, Manuel
Aragonés, Julián
Martínez Estrada, Ofelia María
Soriano Zaragoza, Francesc X. (Francesc Xavier)
Keywords: Malalties cerebrals
Brain diseases
Issue Date: 2-May-2018
Publisher: EMBO Press
Abstract: The formation of neurites is an important process affecting the cognitive abilities of an organism. Neurite growth requires the addition of new membranes, but the metabolic remodeling necessary to supply lipids for membrane expansion is poorly understood. Here, we show that synaptic activity, one of the most important inducers of neurite growth, transcriptionally regulates the expression of neuronal glucose transporter Glut3 and rate-limiting enzymes of glycolysis, resulting in enhanced glucose uptake and metabolism that is partly used for lipid synthesis. Mechanistically, CREB regulates the expression of Glut3 and Siah2, the latter and LDH activity promoting the normoxic stabilization of HIF-1 alpha that regulates the expression of rate-limiting genes of glycolysis. The expression of dominant-negative HIF-1 alpha or Glut3 knockdown blocks activity-dependent neurite growth in vitro while pharmacological inhibition of the glycolysis and specific ablation of HIF-1 alpha in early postnatal mice impairs the neurite architecture. These results suggest that the manipulation of neuronal glucose metabolism could be used to treat some brain developmental disorders.
Note: Versió postprint del document publicat a:
It is part of: The EMBO Journal, 2018, vol. 37, num. 9
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ISSN: 0261-4189
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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