MTORC2 controls actin polymerization required for consolidation of long-term memory

Autores
Huang, Wei; Zhu, Ping Jun; Zhang, Shixing; Zhou, Hongyi; Stoica, Loredana; Galiano, Mauricio Raul; Krnjević, Krešimir; Roman, Gregg; Costa-Mattioli, Mauro
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short-to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.
Fil: Huang, Wei. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Zhu, Ping Jun. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Zhang, Shixing. University Of Houston; Estados Unidos
Fil: Zhou, Hongyi. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Stoica, Loredana. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Galiano, Mauricio Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Krnjević, Krešimir. McGill Universit; Canadá
Fil: Roman, Gregg. University Of Houston; Estados Unidos
Fil: Costa-Mattioli, Mauro. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Materia
Actin Polymerization
Long Term Memory
Mtorc2
Rictor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/79624
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/79624
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MTORC2 controls actin polymerization required for consolidation of long-term memoryHuang, WeiZhu, Ping JunZhang, ShixingZhou, HongyiStoica, LoredanaGaliano, Mauricio RaulKrnjević, KrešimirRoman, GreggCosta-Mattioli, MauroActin PolymerizationLong Term MemoryMtorc2Rictorhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short-to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.Fil: Huang, Wei. Baylor College of Medicine. Department of Neuroscience; Estados UnidosFil: Zhu, Ping Jun. Baylor College of Medicine. Department of Neuroscience; Estados UnidosFil: Zhang, Shixing. University Of Houston; Estados UnidosFil: Zhou, Hongyi. Baylor College of Medicine. Department of Neuroscience; Estados UnidosFil: Stoica, Loredana. Baylor College of Medicine. Department of Neuroscience; Estados UnidosFil: Galiano, Mauricio Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Baylor College of Medicine. Department of Neuroscience; Estados UnidosFil: Krnjević, Krešimir. McGill Universit; CanadáFil: Roman, Gregg. University Of Houston; Estados UnidosFil: Costa-Mattioli, Mauro. Baylor College of Medicine. Department of Neuroscience; Estados UnidosNature Publishing Group2013-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/79624Huang, Wei; Zhu, Ping Jun; Zhang, Shixing; Zhou, Hongyi; Stoica, Loredana; et al.; MTORC2 controls actin polymerization required for consolidation of long-term memory; Nature Publishing Group; Nature Neuroscience.; 16; 4; 4-2013; 441-4481097-62561546-1726CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nn.3351info:eu-repo/semantics/altIdentifier/doi/10.1038/nn.3351info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:28:52Zoai:ri.conicet.gov.ar:11336/79624instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:28:53.101CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MTORC2 controls actin polymerization required for consolidation of long-term memory
title MTORC2 controls actin polymerization required for consolidation of long-term memory
spellingShingle MTORC2 controls actin polymerization required for consolidation of long-term memory
Huang, Wei
Actin Polymerization
Long Term Memory
Mtorc2
Rictor
title_short MTORC2 controls actin polymerization required for consolidation of long-term memory
title_full MTORC2 controls actin polymerization required for consolidation of long-term memory
title_fullStr MTORC2 controls actin polymerization required for consolidation of long-term memory
title_full_unstemmed MTORC2 controls actin polymerization required for consolidation of long-term memory
title_sort MTORC2 controls actin polymerization required for consolidation of long-term memory
dc.creator.none.fl_str_mv Huang, Wei
Zhu, Ping Jun
Zhang, Shixing
Zhou, Hongyi
Stoica, Loredana
Galiano, Mauricio Raul
Krnjević, Krešimir
Roman, Gregg
Costa-Mattioli, Mauro
author Huang, Wei
author_facet Huang, Wei
Zhu, Ping Jun
Zhang, Shixing
Zhou, Hongyi
Stoica, Loredana
Galiano, Mauricio Raul
Krnjević, Krešimir
Roman, Gregg
Costa-Mattioli, Mauro
author_role author
author2 Zhu, Ping Jun
Zhang, Shixing
Zhou, Hongyi
Stoica, Loredana
Galiano, Mauricio Raul
Krnjević, Krešimir
Roman, Gregg
Costa-Mattioli, Mauro
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Actin Polymerization
Long Term Memory
Mtorc2
Rictor
topic Actin Polymerization
Long Term Memory
Mtorc2
Rictor
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short-to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.
Fil: Huang, Wei. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Zhu, Ping Jun. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Zhang, Shixing. University Of Houston; Estados Unidos
Fil: Zhou, Hongyi. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Stoica, Loredana. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Galiano, Mauricio Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
Fil: Krnjević, Krešimir. McGill Universit; Canadá
Fil: Roman, Gregg. University Of Houston; Estados Unidos
Fil: Costa-Mattioli, Mauro. Baylor College of Medicine. Department of Neuroscience; Estados Unidos
description A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short-to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.
publishDate 2013
dc.date.none.fl_str_mv 2013-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/79624
Huang, Wei; Zhu, Ping Jun; Zhang, Shixing; Zhou, Hongyi; Stoica, Loredana; et al.; MTORC2 controls actin polymerization required for consolidation of long-term memory; Nature Publishing Group; Nature Neuroscience.; 16; 4; 4-2013; 441-448
1097-6256
1546-1726
CONICET Digital
CONICET
url http://hdl.handle.net/11336/79624
identifier_str_mv Huang, Wei; Zhu, Ping Jun; Zhang, Shixing; Zhou, Hongyi; Stoica, Loredana; et al.; MTORC2 controls actin polymerization required for consolidation of long-term memory; Nature Publishing Group; Nature Neuroscience.; 16; 4; 4-2013; 441-448
1097-6256
1546-1726
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nn.3351
info:eu-repo/semantics/altIdentifier/doi/10.1038/nn.3351
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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