IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth

IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth

Autor Roffe, Martin Autor UNIFESP Google Scholar
Hajj, Glaucia N. M. Google Scholar
Azevedo, Hatylas Autor UNIFESP Google Scholar
Alves, Viviane S. Autor UNIFESP Google Scholar
Castilho, Beatriz Amaral de Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Hosp AC Camargo Fund Antonio Prudente
Resumo The product of the mouse Imprinted and Ancient gene, IMPACT, is preferentially expressed in neurons. We have previously shown that IMPACT overexpression inhibits the activation of the protein kinase GCN2, which signals amino acid starvation. GCN2 phosphorylates the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2 alpha), resulting in inhibition of general protein synthesis but increased translation of specific messages, such as ATF4. GCN2 is also involved in the regulation of neuronal functions, controlling synaptic plasticity, memory, and feeding behavior. We show here that IMPACT abundance increases during differentiation of neurons and neuron-like N2a cells, whereas GCN2 displays lowered activation levels. Upon differentiation, IMPACT associates with translating ribosomes, enhances translation initiation, and down-regulates the expression of ATF4. We further show that endogenous IMPACT promotes neurite outgrowth whereas GCN2 is a strong inhibitor of spontaneous neuritogenesis. Together, these results uncover the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Data de publicação 2013-04-12
Publicado em Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 288, n. 15, p. 10860-10869, 2013.
ISSN 0021-9258 (Sherpa/Romeo, fator de impacto)
Publicador Amer Soc Biochemistry Molecular Biology Inc
Extensão 10860-10869
Fonte http://dx.doi.org/10.1074/jbc.M113.461970
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000317565000063
Endereço permanente http://repositorio.unifesp.br/handle/11600/36205

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