Molecular function of alpha7 nicotinic receptors

Autores
Bouzat, Cecilia Beatriz
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The α7 nicotinic receptor is expressed in brain and non-neuronal cells. Enhancement of α7 activity by positive allosteric modulators (PAMs) is emerging as a therapeutic strategy for cognitive and inflammatory disorders. We have focused on understanding α7 function and potentiation. We revealed that PAMs enhance α7 activation by increasing the open-channel lifetime and inducing prolonged activation episodes. Although α7 has been considered the homomeric member of the family, a novel α7β2 receptor has been recently discovered in human brain. We generated α7β2 receptors with fixed stoichiometry by two approaches comprising concatenated and unlinked subunits. We found that β2 can assemble with α7 subunits resulting in receptors with different stoichiometries, kinetic signatures and PAM selectivity. This information provides fundamental basis required to decipher the role of α7β2 in native cells. In humans, there is a truncated α7 subunit (dupα7) that lacks part of the ACh-binding site and results from a partial duplication of the α7 gene. Its role remains unknown. We demonstrated that dupα7 acts as a negative modulator, cannot form channels, but can assemble with α7 into functional heteromeric receptors. Deciphering the molecular basis underlying α7 responses has implications for the design of novel therapeutic compounds.
Fil: 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
6th International Iberian Biophysics Congress and X Iberoamerican Congress of Biophysics
Castellon
España
International Iberian Biophysics
Sociedad de Biofísica de España
Materia
NICOTINIC RECEPTOR
ALPHA 7 RECEPTOR
PATCH CLAMP
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:11336/221305

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spelling Molecular function of alpha7 nicotinic receptorsBouzat, Cecilia BeatrizNICOTINIC RECEPTORALPHA 7 RECEPTORPATCH CLAMPhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The α7 nicotinic receptor is expressed in brain and non-neuronal cells. Enhancement of α7 activity by positive allosteric modulators (PAMs) is emerging as a therapeutic strategy for cognitive and inflammatory disorders. We have focused on understanding α7 function and potentiation. We revealed that PAMs enhance α7 activation by increasing the open-channel lifetime and inducing prolonged activation episodes. Although α7 has been considered the homomeric member of the family, a novel α7β2 receptor has been recently discovered in human brain. We generated α7β2 receptors with fixed stoichiometry by two approaches comprising concatenated and unlinked subunits. We found that β2 can assemble with α7 subunits resulting in receptors with different stoichiometries, kinetic signatures and PAM selectivity. This information provides fundamental basis required to decipher the role of α7β2 in native cells. In humans, there is a truncated α7 subunit (dupα7) that lacks part of the ACh-binding site and results from a partial duplication of the α7 gene. Its role remains unknown. We demonstrated that dupα7 acts as a negative modulator, cannot form channels, but can assemble with α7 into functional heteromeric receptors. Deciphering the molecular basis underlying α7 responses has implications for the design of novel therapeutic compounds.Fil: 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; Argentina6th International Iberian Biophysics Congress and X Iberoamerican Congress of BiophysicsCastellonEspañaInternational Iberian BiophysicsSociedad de Biofísica de EspañaSociedad de Biofísica de España2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/221305Molecular function of alpha7 nicotinic receptors; 6th International Iberian Biophysics Congress and X Iberoamerican Congress of Biophysics; Castellon; España; 2018; 55-55CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://biofisica.info/6th-iberian-10th-iberoamerican-biophysics-congress/info:eu-repo/semantics/altIdentifier/url/https://www.uv.es/biophys/sbe/S/book_of_abstracts_S2.pdfInternacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:16Zoai:ri.conicet.gov.ar:11336/221305instacron: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:34982025-09-03 10:10:17.301CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular function of alpha7 nicotinic receptors
title Molecular function of alpha7 nicotinic receptors
spellingShingle Molecular function of alpha7 nicotinic receptors
Bouzat, Cecilia Beatriz
NICOTINIC RECEPTOR
ALPHA 7 RECEPTOR
PATCH CLAMP
title_short Molecular function of alpha7 nicotinic receptors
title_full Molecular function of alpha7 nicotinic receptors
title_fullStr Molecular function of alpha7 nicotinic receptors
title_full_unstemmed Molecular function of alpha7 nicotinic receptors
title_sort Molecular function of alpha7 nicotinic receptors
dc.creator.none.fl_str_mv Bouzat, Cecilia Beatriz
author Bouzat, Cecilia Beatriz
author_facet Bouzat, Cecilia Beatriz
author_role author
dc.subject.none.fl_str_mv NICOTINIC RECEPTOR
ALPHA 7 RECEPTOR
PATCH CLAMP
topic NICOTINIC RECEPTOR
ALPHA 7 RECEPTOR
PATCH CLAMP
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 receptor is expressed in brain and non-neuronal cells. Enhancement of α7 activity by positive allosteric modulators (PAMs) is emerging as a therapeutic strategy for cognitive and inflammatory disorders. We have focused on understanding α7 function and potentiation. We revealed that PAMs enhance α7 activation by increasing the open-channel lifetime and inducing prolonged activation episodes. Although α7 has been considered the homomeric member of the family, a novel α7β2 receptor has been recently discovered in human brain. We generated α7β2 receptors with fixed stoichiometry by two approaches comprising concatenated and unlinked subunits. We found that β2 can assemble with α7 subunits resulting in receptors with different stoichiometries, kinetic signatures and PAM selectivity. This information provides fundamental basis required to decipher the role of α7β2 in native cells. In humans, there is a truncated α7 subunit (dupα7) that lacks part of the ACh-binding site and results from a partial duplication of the α7 gene. Its role remains unknown. We demonstrated that dupα7 acts as a negative modulator, cannot form channels, but can assemble with α7 into functional heteromeric receptors. Deciphering the molecular basis underlying α7 responses has implications for the design of novel therapeutic compounds.
Fil: 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
6th International Iberian Biophysics Congress and X Iberoamerican Congress of Biophysics
Castellon
España
International Iberian Biophysics
Sociedad de Biofísica de España
description The α7 nicotinic receptor is expressed in brain and non-neuronal cells. Enhancement of α7 activity by positive allosteric modulators (PAMs) is emerging as a therapeutic strategy for cognitive and inflammatory disorders. We have focused on understanding α7 function and potentiation. We revealed that PAMs enhance α7 activation by increasing the open-channel lifetime and inducing prolonged activation episodes. Although α7 has been considered the homomeric member of the family, a novel α7β2 receptor has been recently discovered in human brain. We generated α7β2 receptors with fixed stoichiometry by two approaches comprising concatenated and unlinked subunits. We found that β2 can assemble with α7 subunits resulting in receptors with different stoichiometries, kinetic signatures and PAM selectivity. This information provides fundamental basis required to decipher the role of α7β2 in native cells. In humans, there is a truncated α7 subunit (dupα7) that lacks part of the ACh-binding site and results from a partial duplication of the α7 gene. Its role remains unknown. We demonstrated that dupα7 acts as a negative modulator, cannot form channels, but can assemble with α7 into functional heteromeric receptors. Deciphering the molecular basis underlying α7 responses has implications for the design of novel therapeutic compounds.
publishDate 2018
dc.date.none.fl_str_mv 2018
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/11336/221305
Molecular function of alpha7 nicotinic receptors; 6th International Iberian Biophysics Congress and X Iberoamerican Congress of Biophysics; Castellon; España; 2018; 55-55
CONICET Digital
CONICET
url http://hdl.handle.net/11336/221305
identifier_str_mv Molecular function of alpha7 nicotinic receptors; 6th International Iberian Biophysics Congress and X Iberoamerican Congress of Biophysics; Castellon; España; 2018; 55-55
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://biofisica.info/6th-iberian-10th-iberoamerican-biophysics-congress/
info:eu-repo/semantics/altIdentifier/url/https://www.uv.es/biophys/sbe/S/book_of_abstracts_S2.pdf
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
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedad de Biofísica de España
publisher.none.fl_str_mv Sociedad de Biofísica de España
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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