Functional and structural characterization of human heteromeric 5-HT3 receptors

Autores
Mazzarini Dimarco, Albano; Bouzat, Cecilia Beatriz; Corradi, Jeremias
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
5 HT3 receptors are the only serotonin (5-HT) receptors that belong to the Cys-loop receptor family. They mediate fast excitatory transmission in central and peripheral nervous system. Five different subunits (A-E) have been identified in humans. The A subunit is able to form homomeric receptors (5-HT3A), and it can combine with the B subunit to form heteromeric receptors. We here evaluated if the C-E subunits can combine with the A to form heteromeric receptors. To this end, we constructed a high-conductance A subunit (AHC) that allowed to obtain single-channel events. After expression of the AHC we observed events with an amplitude of ~4.7 pA corresponding to the 5 HT3AHC receptor. However, when AHC was expressed in combination with one of the CE subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. From macroscopic currents we observed an increase in the 5-HT EC50 value for each of the heteromeric receptors with respect to that for the 5 HT3AHC receptor. In-silico studies provided insights into the contribution of the different subunits to the 5-HT binding site. Our results demonstrate that C-E subunits can combine with the A subunit to form heteromeric receptors. These results bring structural and functional details about the different human 5-HT3 receptors and will contribute to the development of selective therapies targeting this receptor family.
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN)
Villa Carlos Paz
Argentina
Sociedad Argentina de Investigación en Neurociencias.
Materia
SEROTONIN
HETEROMERIC
TYPE 3
SUBUNITS
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:11336/192235
Acceder
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spelling Functional and structural characterization of human heteromeric 5-HT3 receptorsMazzarini Dimarco, AlbanoBouzat, Cecilia BeatrizCorradi, JeremiasSEROTONINHETEROMERICTYPE 3SUBUNITShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/15 HT3 receptors are the only serotonin (5-HT) receptors that belong to the Cys-loop receptor family. They mediate fast excitatory transmission in central and peripheral nervous system. Five different subunits (A-E) have been identified in humans. The A subunit is able to form homomeric receptors (5-HT3A), and it can combine with the B subunit to form heteromeric receptors. We here evaluated if the C-E subunits can combine with the A to form heteromeric receptors. To this end, we constructed a high-conductance A subunit (AHC) that allowed to obtain single-channel events. After expression of the AHC we observed events with an amplitude of ~4.7 pA corresponding to the 5 HT3AHC receptor. However, when AHC was expressed in combination with one of the CE subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. From macroscopic currents we observed an increase in the 5-HT EC50 value for each of the heteromeric receptors with respect to that for the 5 HT3AHC receptor. In-silico studies provided insights into the contribution of the different subunits to the 5-HT binding site. Our results demonstrate that C-E subunits can combine with the A subunit to form heteromeric receptors. These results bring structural and functional details about the different human 5-HT3 receptors and will contribute to the development of selective therapies targeting this receptor family.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. 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; 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; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaXXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN)Villa Carlos PazArgentinaSociedad Argentina de Investigación en Neurociencias.Sociedad Argentina de Investigación en Neurociencias (SAN)2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/192235Functional and structural characterization of human heteromeric 5-HT3 receptors; XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); Villa Carlos Paz; Argentina; 2019; 65-66CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saneurociencias.org.ar/congresos-san-2/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 Técnicas2025-09-03T09:57:57Zoai:ri.conicet.gov.ar:11336/192235instacron: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 09:57:57.948CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional and structural characterization of human heteromeric 5-HT3 receptors
title Functional and structural characterization of human heteromeric 5-HT3 receptors
spellingShingle Functional and structural characterization of human heteromeric 5-HT3 receptors
Mazzarini Dimarco, Albano
SEROTONIN
HETEROMERIC
TYPE 3
SUBUNITS
title_short Functional and structural characterization of human heteromeric 5-HT3 receptors
title_full Functional and structural characterization of human heteromeric 5-HT3 receptors
title_fullStr Functional and structural characterization of human heteromeric 5-HT3 receptors
title_full_unstemmed Functional and structural characterization of human heteromeric 5-HT3 receptors
title_sort Functional and structural characterization of human heteromeric 5-HT3 receptors
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 SEROTONIN
HETEROMERIC
TYPE 3
SUBUNITS
topic SEROTONIN
HETEROMERIC
TYPE 3
SUBUNITS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 5 HT3 receptors are the only serotonin (5-HT) receptors that belong to the Cys-loop receptor family. They mediate fast excitatory transmission in central and peripheral nervous system. Five different subunits (A-E) have been identified in humans. The A subunit is able to form homomeric receptors (5-HT3A), and it can combine with the B subunit to form heteromeric receptors. We here evaluated if the C-E subunits can combine with the A to form heteromeric receptors. To this end, we constructed a high-conductance A subunit (AHC) that allowed to obtain single-channel events. After expression of the AHC we observed events with an amplitude of ~4.7 pA corresponding to the 5 HT3AHC receptor. However, when AHC was expressed in combination with one of the CE subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. From macroscopic currents we observed an increase in the 5-HT EC50 value for each of the heteromeric receptors with respect to that for the 5 HT3AHC receptor. In-silico studies provided insights into the contribution of the different subunits to the 5-HT binding site. Our results demonstrate that C-E subunits can combine with the A subunit to form heteromeric receptors. These results bring structural and functional details about the different human 5-HT3 receptors and will contribute to the development of selective therapies targeting this receptor family.
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN)
Villa Carlos Paz
Argentina
Sociedad Argentina de Investigación en Neurociencias.
description 5 HT3 receptors are the only serotonin (5-HT) receptors that belong to the Cys-loop receptor family. They mediate fast excitatory transmission in central and peripheral nervous system. Five different subunits (A-E) have been identified in humans. The A subunit is able to form homomeric receptors (5-HT3A), and it can combine with the B subunit to form heteromeric receptors. We here evaluated if the C-E subunits can combine with the A to form heteromeric receptors. To this end, we constructed a high-conductance A subunit (AHC) that allowed to obtain single-channel events. After expression of the AHC we observed events with an amplitude of ~4.7 pA corresponding to the 5 HT3AHC receptor. However, when AHC was expressed in combination with one of the CE subunits, events with different amplitudes were detected, thus confirming the expression of heteromeric receptors. From macroscopic currents we observed an increase in the 5-HT EC50 value for each of the heteromeric receptors with respect to that for the 5 HT3AHC receptor. In-silico studies provided insights into the contribution of the different subunits to the 5-HT binding site. Our results demonstrate that C-E subunits can combine with the A subunit to form heteromeric receptors. These results bring structural and functional details about the different human 5-HT3 receptors and will contribute to the development of selective therapies targeting this receptor family.
publishDate 2019
dc.date.none.fl_str_mv 2019
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/11336/192235
Functional and structural characterization of human heteromeric 5-HT3 receptors; XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); Villa Carlos Paz; Argentina; 2019; 65-66
CONICET Digital
CONICET
url http://hdl.handle.net/11336/192235
identifier_str_mv Functional and structural characterization of human heteromeric 5-HT3 receptors; XXXIV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); Villa Carlos Paz; Argentina; 2019; 65-66
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://saneurociencias.org.ar/congresos-san-2/
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
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application/pdf
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias (SAN)
publisher.none.fl_str_mv Sociedad Argentina de Investigación en Neurociencias (SAN)
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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