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

Detalhes bibliográficos
Autor(a) principal: Roffe, Martin [UNIFESP]
Data de Publicação: 2013
Outros Autores: Hajj, Glaucia N. M., Azevedo, Hatylas [UNIFESP], Alves, Viviane S. [UNIFESP], Castilho, Beatriz Amaral de [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
dARK ID: ark:/48912/001300000gw38
Texto Completo: http://dx.doi.org/10.1074/jbc.M113.461970
http://repositorio.unifesp.br/handle/11600/36205
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.
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spelling IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite OutgrowthThe 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.Universidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, BR-04023062 São Paulo, BrazilHosp AC Camargo Fund Antonio Prudente, Int Res Ctr, Natl Inst Translat Neurosci, BR-01509010 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, BR-04023062 São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Amer Soc Biochemistry Molecular Biology IncUniversidade Federal de São Paulo (UNIFESP)Hosp AC Camargo Fund Antonio PrudenteRoffe, Martin [UNIFESP]Hajj, Glaucia N. M.Azevedo, Hatylas [UNIFESP]Alves, Viviane S. [UNIFESP]Castilho, Beatriz Amaral de [UNIFESP]2016-01-24T14:31:34Z2016-01-24T14:31:34Z2013-04-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10860-10869http://dx.doi.org/10.1074/jbc.M113.461970Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 288, n. 15, p. 10860-10869, 2013.10.1074/jbc.M113.461970WOS000317565000063.pdf0021-9258http://repositorio.unifesp.br/handle/11600/36205WOS:000317565000063ark:/48912/001300000gw38engJournal of Biological Chemistryinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2023-05-18T13:49:24Zoai:repositorio.unifesp.br/:11600/36205Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:17:50.520862Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth
title IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth
spellingShingle IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth
Roffe, Martin [UNIFESP]
title_short IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth
title_full IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth
title_fullStr IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth
title_full_unstemmed IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth
title_sort IMPACT Is a Developmentally Regulated Protein in Neurons That Opposes the Eukaryotic Initiation Factor 2 alpha Kinase GCN2 in the modulation of Neurite Outgrowth
author Roffe, Martin [UNIFESP]
author_facet Roffe, Martin [UNIFESP]
Hajj, Glaucia N. M.
Azevedo, Hatylas [UNIFESP]
Alves, Viviane S. [UNIFESP]
Castilho, Beatriz Amaral de [UNIFESP]
author_role author
author2 Hajj, Glaucia N. M.
Azevedo, Hatylas [UNIFESP]
Alves, Viviane S. [UNIFESP]
Castilho, Beatriz Amaral de [UNIFESP]
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
Hosp AC Camargo Fund Antonio Prudente
dc.contributor.author.fl_str_mv Roffe, Martin [UNIFESP]
Hajj, Glaucia N. M.
Azevedo, Hatylas [UNIFESP]
Alves, Viviane S. [UNIFESP]
Castilho, Beatriz Amaral de [UNIFESP]
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013-04-12
2016-01-24T14:31:34Z
2016-01-24T14:31:34Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1074/jbc.M113.461970
Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 288, n. 15, p. 10860-10869, 2013.
10.1074/jbc.M113.461970
WOS000317565000063.pdf
0021-9258
http://repositorio.unifesp.br/handle/11600/36205
WOS:000317565000063
dc.identifier.dark.fl_str_mv ark:/48912/001300000gw38
url http://dx.doi.org/10.1074/jbc.M113.461970
http://repositorio.unifesp.br/handle/11600/36205
identifier_str_mv Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 288, n. 15, p. 10860-10869, 2013.
10.1074/jbc.M113.461970
WOS000317565000063.pdf
0021-9258
WOS:000317565000063
ark:/48912/001300000gw38
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Biological Chemistry
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10860-10869
dc.publisher.none.fl_str_mv Amer Soc Biochemistry Molecular Biology Inc
publisher.none.fl_str_mv Amer Soc Biochemistry Molecular Biology Inc
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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