Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses

Autores
Chrestia, Juan Facundo
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The α7 nicotinic acetylcholine receptor in neurons is associated to neurological and neurodegenerative disorders. α7 is also expressed in glial and immune cells, where it plays a role in neuroprotection and inflammation. Protein phosphorylation is an important regulatory mechanism involved in physiological and pathological processes. We investigated the role of tyrosine phosphorylation of α7 in its dual ionotropic/metabotropic function. In cells expressing α7, singlechannel activity appears as brief isolated openings and episodes of few openings in quick succession (bursts). Inhibition of Src family kinases by PP2 as well as co-expression of α7 with an inactive Src kinase increase the duration and frequency of bursts, while inhibition of tyrosine phosphatases decreases open and burst durations without affecting channel amplitude. A mutant α7 lacking phosphorylation sites shows longer burst durations and insensitivity to PP2, thus revealing that the two tyrosine residues in the intracellular domain (ICD) are involved in receptor modulation. Cells exposed to a specific α7 agonist show an increase of ERK1/2 phosphorylation, which is detected neither in the presence of Src family kinases inhibitors nor in cells expressing the mutant receptor lacking tyrosines. Thus, phosphorylation negatively modulates ionotropic α7 activity probably by enhancing desensitization whereas the phosphorylated state of α7-ICD is required for the metabotropic receptor responses.
Fil: Chrestia, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XXXV Reunión Anual Virtual de la Sociedad Argentina de Investigación en Neurociencias
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
NICOTINIC ACETYLCHOLINE RECEPTOR
TYROSINE
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:11336/192238
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/192238
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responsesChrestia, Juan FacundoNICOTINIC ACETYLCHOLINE RECEPTORTYROSINEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The α7 nicotinic acetylcholine receptor in neurons is associated to neurological and neurodegenerative disorders. α7 is also expressed in glial and immune cells, where it plays a role in neuroprotection and inflammation. Protein phosphorylation is an important regulatory mechanism involved in physiological and pathological processes. We investigated the role of tyrosine phosphorylation of α7 in its dual ionotropic/metabotropic function. In cells expressing α7, singlechannel activity appears as brief isolated openings and episodes of few openings in quick succession (bursts). Inhibition of Src family kinases by PP2 as well as co-expression of α7 with an inactive Src kinase increase the duration and frequency of bursts, while inhibition of tyrosine phosphatases decreases open and burst durations without affecting channel amplitude. A mutant α7 lacking phosphorylation sites shows longer burst durations and insensitivity to PP2, thus revealing that the two tyrosine residues in the intracellular domain (ICD) are involved in receptor modulation. Cells exposed to a specific α7 agonist show an increase of ERK1/2 phosphorylation, which is detected neither in the presence of Src family kinases inhibitors nor in cells expressing the mutant receptor lacking tyrosines. Thus, phosphorylation negatively modulates ionotropic α7 activity probably by enhancing desensitization whereas the phosphorylated state of α7-ICD is required for the metabotropic receptor responses.Fil: Chrestia, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaXXXV Reunión Anual Virtual de la Sociedad Argentina de Investigación en NeurocienciasArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Neurociencias2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/192238Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses; XXXV Reunión Anual Virtual de la Sociedad Argentina de Investigación en Neurociencias; Argentina; 2020; 52-62CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://csan2020.saneurociencias.org.ar/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:32:43Zoai:ri.conicet.gov.ar:11336/192238instacron: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:34982025-09-29 09:32:43.893CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses
title Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses
spellingShingle Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses
Chrestia, Juan Facundo
NICOTINIC ACETYLCHOLINE RECEPTOR
TYROSINE
title_short Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses
title_full Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses
title_fullStr Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses
title_full_unstemmed Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses
title_sort Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses
dc.creator.none.fl_str_mv Chrestia, Juan Facundo
author Chrestia, Juan Facundo
author_facet Chrestia, Juan Facundo
author_role author
dc.subject.none.fl_str_mv NICOTINIC ACETYLCHOLINE RECEPTOR
TYROSINE
topic NICOTINIC ACETYLCHOLINE RECEPTOR
TYROSINE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The α7 nicotinic acetylcholine receptor in neurons is associated to neurological and neurodegenerative disorders. α7 is also expressed in glial and immune cells, where it plays a role in neuroprotection and inflammation. Protein phosphorylation is an important regulatory mechanism involved in physiological and pathological processes. We investigated the role of tyrosine phosphorylation of α7 in its dual ionotropic/metabotropic function. In cells expressing α7, singlechannel activity appears as brief isolated openings and episodes of few openings in quick succession (bursts). Inhibition of Src family kinases by PP2 as well as co-expression of α7 with an inactive Src kinase increase the duration and frequency of bursts, while inhibition of tyrosine phosphatases decreases open and burst durations without affecting channel amplitude. A mutant α7 lacking phosphorylation sites shows longer burst durations and insensitivity to PP2, thus revealing that the two tyrosine residues in the intracellular domain (ICD) are involved in receptor modulation. Cells exposed to a specific α7 agonist show an increase of ERK1/2 phosphorylation, which is detected neither in the presence of Src family kinases inhibitors nor in cells expressing the mutant receptor lacking tyrosines. Thus, phosphorylation negatively modulates ionotropic α7 activity probably by enhancing desensitization whereas the phosphorylated state of α7-ICD is required for the metabotropic receptor responses.
Fil: Chrestia, Juan Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XXXV Reunión Anual Virtual de la Sociedad Argentina de Investigación en Neurociencias
Argentina
Sociedad Argentina de Investigación en Neurociencias
description The α7 nicotinic acetylcholine receptor in neurons is associated to neurological and neurodegenerative disorders. α7 is also expressed in glial and immune cells, where it plays a role in neuroprotection and inflammation. Protein phosphorylation is an important regulatory mechanism involved in physiological and pathological processes. We investigated the role of tyrosine phosphorylation of α7 in its dual ionotropic/metabotropic function. In cells expressing α7, singlechannel activity appears as brief isolated openings and episodes of few openings in quick succession (bursts). Inhibition of Src family kinases by PP2 as well as co-expression of α7 with an inactive Src kinase increase the duration and frequency of bursts, while inhibition of tyrosine phosphatases decreases open and burst durations without affecting channel amplitude. A mutant α7 lacking phosphorylation sites shows longer burst durations and insensitivity to PP2, thus revealing that the two tyrosine residues in the intracellular domain (ICD) are involved in receptor modulation. Cells exposed to a specific α7 agonist show an increase of ERK1/2 phosphorylation, which is detected neither in the presence of Src family kinases inhibitors nor in cells expressing the mutant receptor lacking tyrosines. Thus, phosphorylation negatively modulates ionotropic α7 activity probably by enhancing desensitization whereas the phosphorylated state of α7-ICD is required for the metabotropic receptor responses.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/192238
Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses; XXXV Reunión Anual Virtual de la Sociedad Argentina de Investigación en Neurociencias; Argentina; 2020; 52-62
CONICET Digital
CONICET
url http://hdl.handle.net/11336/192238
identifier_str_mv Specific tyrosine phosphorylation of α7 nicotinic receptor modulates its ionotropic and metabotropic responses; XXXV Reunión Anual Virtual de la Sociedad Argentina de Investigación en Neurociencias; Argentina; 2020; 52-62
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://csan2020.saneurociencias.org.ar/
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/
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Neurociencias
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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