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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/221305
Ver los metadatos del registro completo
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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 |
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info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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openAccess |
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https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
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application/pdf application/pdf application/pdf |
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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 |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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