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(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , |
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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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 |
_version_ |
1818602463658246144 |