Human 5-HT3 receptors: Structural and functional features

Autores
Mazzarini Dimarco, Albano; Bouzat, Cecilia Beatriz; Corradi, Jeremias
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The 5-HT3 receptor is a ligand-gated ion channel that converts the binding of serotonin (5-HT) into a transient cation current which mediates fast excitatory responses in peripheral and central nervous systems. Five human subunits (A-E) have been identified to date. The A subunit can assemble to form homomeric receptors (5-HT3A), or combine with B-E subunits to form heteromeric receptors (5-HT3AB-E). To determine subunit composition and stoichiometry of heteromeric receptors we constructed a high conductance A subunit (AHC), which allowed us to detect single-channel events, and expressed the AHC with C, D or E subunits. From macroscopic currents we observed an increase in the 5-HT EC50 values for all subunit combinations with respect to that of 5- HT3AHC. Expression of the AHC to form 5-HT3AHC receptors showed opening events of homogeneous amplitudes. However, when AHC was expressed in combination with one of the C-E subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. In-silico studies provided insights into the contribution of the different subunits to the binding site conformation. Thus, our results confirm that C-E subunits can combine with the A subunit to form heteromeric receptors, and bring structural and functional details about the different human 5-HT3 receptors that can be expressed.
Fil: Mazzarini Dimarco, Albano. 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
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
Fil: Corradi, Jeremias. 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
XXXV Annual Meeting of the Argentinian Society for Neuroscience Research
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
5-ht3 RECEPTORS
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:11336/155874
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Human 5-HT3 receptors: Structural and functional featuresMazzarini Dimarco, AlbanoBouzat, Cecilia BeatrizCorradi, Jeremias5-ht3 RECEPTORShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The 5-HT3 receptor is a ligand-gated ion channel that converts the binding of serotonin (5-HT) into a transient cation current which mediates fast excitatory responses in peripheral and central nervous systems. Five human subunits (A-E) have been identified to date. The A subunit can assemble to form homomeric receptors (5-HT3A), or combine with B-E subunits to form heteromeric receptors (5-HT3AB-E). To determine subunit composition and stoichiometry of heteromeric receptors we constructed a high conductance A subunit (AHC), which allowed us to detect single-channel events, and expressed the AHC with C, D or E subunits. From macroscopic currents we observed an increase in the 5-HT EC50 values for all subunit combinations with respect to that of 5- HT3AHC. Expression of the AHC to form 5-HT3AHC receptors showed opening events of homogeneous amplitudes. However, when AHC was expressed in combination with one of the C-E subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. In-silico studies provided insights into the contribution of the different subunits to the binding site conformation. Thus, our results confirm that C-E subunits can combine with the A subunit to form heteromeric receptors, and bring structural and functional details about the different human 5-HT3 receptors that can be expressed.Fil: Mazzarini Dimarco, Albano. 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; 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; ArgentinaFil: Corradi, Jeremias. 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; ArgentinaXXXV Annual Meeting of the Argentinian Society for Neuroscience ResearchArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Investigación en Neurociencias2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/155874Human 5-HT3 receptors: Structural and functional features; XXXV Annual Meeting of the Argentinian Society for Neuroscience Research; Argentina; 2020; 86-86CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://san2020.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 Técnicas2025-09-10T13:20:41Zoai:ri.conicet.gov.ar:11336/155874instacron: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:34982025-09-10 13:20:41.665CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Human 5-HT3 receptors: Structural and functional features
title Human 5-HT3 receptors: Structural and functional features
spellingShingle Human 5-HT3 receptors: Structural and functional features
Mazzarini Dimarco, Albano
5-ht3 RECEPTORS
title_short Human 5-HT3 receptors: Structural and functional features
title_full Human 5-HT3 receptors: Structural and functional features
title_fullStr Human 5-HT3 receptors: Structural and functional features
title_full_unstemmed Human 5-HT3 receptors: Structural and functional features
title_sort Human 5-HT3 receptors: Structural and functional features
dc.creator.none.fl_str_mv Mazzarini Dimarco, Albano
Bouzat, Cecilia Beatriz
Corradi, Jeremias
author Mazzarini Dimarco, Albano
author_facet Mazzarini Dimarco, Albano
Bouzat, Cecilia Beatriz
Corradi, Jeremias
author_role author
author2 Bouzat, Cecilia Beatriz
Corradi, Jeremias
author2_role author
author
dc.subject.none.fl_str_mv 5-ht3 RECEPTORS
topic 5-ht3 RECEPTORS
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 5-HT3 receptor is a ligand-gated ion channel that converts the binding of serotonin (5-HT) into a transient cation current which mediates fast excitatory responses in peripheral and central nervous systems. Five human subunits (A-E) have been identified to date. The A subunit can assemble to form homomeric receptors (5-HT3A), or combine with B-E subunits to form heteromeric receptors (5-HT3AB-E). To determine subunit composition and stoichiometry of heteromeric receptors we constructed a high conductance A subunit (AHC), which allowed us to detect single-channel events, and expressed the AHC with C, D or E subunits. From macroscopic currents we observed an increase in the 5-HT EC50 values for all subunit combinations with respect to that of 5- HT3AHC. Expression of the AHC to form 5-HT3AHC receptors showed opening events of homogeneous amplitudes. However, when AHC was expressed in combination with one of the C-E subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. In-silico studies provided insights into the contribution of the different subunits to the binding site conformation. Thus, our results confirm that C-E subunits can combine with the A subunit to form heteromeric receptors, and bring structural and functional details about the different human 5-HT3 receptors that can be expressed.
Fil: Mazzarini Dimarco, Albano. 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
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
Fil: Corradi, Jeremias. 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
XXXV Annual Meeting of the Argentinian Society for Neuroscience Research
Argentina
Sociedad Argentina de Investigación en Neurociencias
description The 5-HT3 receptor is a ligand-gated ion channel that converts the binding of serotonin (5-HT) into a transient cation current which mediates fast excitatory responses in peripheral and central nervous systems. Five human subunits (A-E) have been identified to date. The A subunit can assemble to form homomeric receptors (5-HT3A), or combine with B-E subunits to form heteromeric receptors (5-HT3AB-E). To determine subunit composition and stoichiometry of heteromeric receptors we constructed a high conductance A subunit (AHC), which allowed us to detect single-channel events, and expressed the AHC with C, D or E subunits. From macroscopic currents we observed an increase in the 5-HT EC50 values for all subunit combinations with respect to that of 5- HT3AHC. Expression of the AHC to form 5-HT3AHC receptors showed opening events of homogeneous amplitudes. However, when AHC was expressed in combination with one of the C-E subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. In-silico studies provided insights into the contribution of the different subunits to the binding site conformation. Thus, our results confirm that C-E subunits can combine with the A subunit to form heteromeric receptors, and bring structural and functional details about the different human 5-HT3 receptors that can be expressed.
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
Reunión
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/11336/155874
Human 5-HT3 receptors: Structural and functional features; XXXV Annual Meeting of the Argentinian Society for Neuroscience Research; Argentina; 2020; 86-86
CONICET Digital
CONICET
url http://hdl.handle.net/11336/155874
identifier_str_mv Human 5-HT3 receptors: Structural and functional features; XXXV Annual Meeting of the Argentinian Society for Neuroscience Research; Argentina; 2020; 86-86
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://san2020.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/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias
publisher.none.fl_str_mv Sociedad Argentina de Investigación en 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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