Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor

The α7 nicotinic acetylcholine receptor is involved in neurological, neurodegenerative, and inflammatory disorders. It operates both as a ligand-gated cationic channel and as a metabotropic receptor in neuronal and non-neuronal cells. As protein phosphorylation is an important cell function regulato...

ver descrição completa

Detalhes bibliográficos
Autores: Chrestia, Juan Facundo, Bruzzone, Ariana, Esandi, María del Carmen, Bouzat, Cecilia Beatriz
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/136315
Acesso em linha:http://hdl.handle.net/11336/136315
Access Level:acceso abierto
Palavra-chave:CYS-LOOP RECEPTORS
DESENSITIZATION
PATCH-CLAMP
SINGLE-CHANNEL RECORDINGS
SRC-FAMILY KINASES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
id AR_eb8b998e2488dc05f4e1ea5851a18fef
oai_identifier_str oai:ri.conicet.gov.ar:11336/136315
network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
title Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
spellingShingle Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
Chrestia, Juan Facundo
CYS-LOOP RECEPTORS
DESENSITIZATION
PATCH-CLAMP
SINGLE-CHANNEL RECORDINGS
SRC-FAMILY KINASES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
title_short Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
title_full Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
title_fullStr Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
title_full_unstemmed Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
title_sort Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
dc.creator.none.fl_str_mv Chrestia, Juan Facundo
Bruzzone, Ariana
Esandi, María del Carmen
Bouzat, Cecilia Beatriz
author Chrestia, Juan Facundo
author_facet Chrestia, Juan Facundo
Bruzzone, Ariana
Esandi, María del Carmen
Bouzat, Cecilia Beatriz
author_role author
author2 Bruzzone, Ariana
Esandi, María del Carmen
Bouzat, Cecilia Beatriz
author2_role author
author
author
dc.subject.none.fl_str_mv CYS-LOOP RECEPTORS
DESENSITIZATION
PATCH-CLAMP
SINGLE-CHANNEL RECORDINGS
SRC-FAMILY KINASES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic CYS-LOOP RECEPTORS
DESENSITIZATION
PATCH-CLAMP
SINGLE-CHANNEL RECORDINGS
SRC-FAMILY KINASES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
description The α7 nicotinic acetylcholine receptor is involved in neurological, neurodegenerative, and inflammatory disorders. It operates both as a ligand-gated cationic channel and as a metabotropic receptor in neuronal and non-neuronal cells. As protein phosphorylation is an important cell function regulatory mechanism, deciphering how tyrosine phosphorylation modulates α7 dual ionotropic/metabotropic molecular function is required for understanding its integral role in physiological and pathological processes. α7 single-channel activity elicited by ACh appears as brief isolated openings and less often as episodes of few openings in quick succession. The reduction of phosphorylation by tyrosine kinase inhibition increases the duration and frequency of activation episodes, whereas the inhibition of phosphatases has the opposite effect. Removal of two tyrosine residues at the α7 intracellular domain recapitulates the effects mediated by tyrosine kinase inhibition. The tyrosine-free mutant receptor shows longer duration-activation episodes, reduced desensitization rate and significantly faster recovery from desensitization, indicating that phosphorylation decreases α7 channel activity by favoring the desensitized state. However, the mutant receptor is incapable of triggering ERK1/2 phosphorylation in response to the α7-agonist. Thus, while tyrosine phosphorylation is absolutely required for α7-triggered ERK pathway, it negatively modulates α7 ionotropic activity. Overall, phosphorylation/dephosphorylation events fine-tune the integrated cell response mediated by α7 activation, thus having a broad impact on α7 cholinergic signaling.
publishDate 2021
dc.date.none.fl_str_mv 2021-05-24
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/11336/136315
Chrestia, Juan Facundo; Bruzzone, Ariana; Esandi, María del Carmen; Bouzat, Cecilia Beatriz; Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor; Springer Nature Switzerland; Cellular and Molecular Life Sciences; 78; 24-5-2021; 5381–5395
1420-682X
1420-9071
CONICET Digital
CONICET
url http://hdl.handle.net/11336/136315
identifier_str_mv Chrestia, Juan Facundo; Bruzzone, Ariana; Esandi, María del Carmen; Bouzat, Cecilia Beatriz; Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor; Springer Nature Switzerland; Cellular and Molecular Life Sciences; 78; 24-5-2021; 5381–5395
1420-682X
1420-9071
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://link.springer.com/article/10.1007%2Fs00018-021-03853-3
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00018-021-03853-3
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer Nature Switzerland
publisher.none.fl_str_mv Springer Nature Switzerland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
_version_ 1799194810674839552
spelling Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptorChrestia, Juan FacundoBruzzone, ArianaEsandi, María del CarmenBouzat, Cecilia BeatrizCYS-LOOP RECEPTORSDESENSITIZATIONPATCH-CLAMPSINGLE-CHANNEL RECORDINGSSRC-FAMILY KINASEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The α7 nicotinic acetylcholine receptor is involved in neurological, neurodegenerative, and inflammatory disorders. It operates both as a ligand-gated cationic channel and as a metabotropic receptor in neuronal and non-neuronal cells. As protein phosphorylation is an important cell function regulatory mechanism, deciphering how tyrosine phosphorylation modulates α7 dual ionotropic/metabotropic molecular function is required for understanding its integral role in physiological and pathological processes. α7 single-channel activity elicited by ACh appears as brief isolated openings and less often as episodes of few openings in quick succession. The reduction of phosphorylation by tyrosine kinase inhibition increases the duration and frequency of activation episodes, whereas the inhibition of phosphatases has the opposite effect. Removal of two tyrosine residues at the α7 intracellular domain recapitulates the effects mediated by tyrosine kinase inhibition. The tyrosine-free mutant receptor shows longer duration-activation episodes, reduced desensitization rate and significantly faster recovery from desensitization, indicating that phosphorylation decreases α7 channel activity by favoring the desensitized state. However, the mutant receptor is incapable of triggering ERK1/2 phosphorylation in response to the α7-agonist. Thus, while tyrosine phosphorylation is absolutely required for α7-triggered ERK pathway, it negatively modulates α7 ionotropic activity. Overall, phosphorylation/dephosphorylation events fine-tune the integrated cell response mediated by α7 activation, thus having a broad impact on α7 cholinergic signaling.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; ArgentinaFil: Bruzzone, Ariana. 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; ArgentinaFil: Esandi, María del Carmen. 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; ArgentinaFil: Bouzat, Cecilia Beatriz. 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; ArgentinaSpringer Nature Switzerland2021-05-24info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/136315Chrestia, Juan Facundo; Bruzzone, Ariana; Esandi, María del Carmen; Bouzat, Cecilia Beatriz; Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor; Springer Nature Switzerland; Cellular and Molecular Life Sciences; 78; 24-5-2021; 5381–53951420-682X1420-9071CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00018-021-03853-3info:eu-repo/semantics/altIdentifier/doi/10.1007/s00018-021-03853-3info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:36:57Zoai:ri.conicet.gov.ar:11336/136315instacron: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:34982024-05-08 13:36:57.372CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
score 15,812429

Registos relacionados