Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs

Autores
Turani, Ornella; Hernando, Guillermina Silvana; Bouzat, Cecilia Beatriz
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
The free-living nematode Caenorhabditis elegans is a model of parasitic nematodes. This worm has the most extensive family of Cys-loop receptors, which are pentameric ligand- gated ion channels that include nicotinic receptors (nAChRs). C. elegans contains an extended family of nAChRs but the functional properties and roles of many of these nAChRs remain unknown. ACR-23 is a nAChR present in neuronal and muscle cells of nematodes and is not conserved in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), a new anthelmintic drug. Given the limited information about its functional role in nematodes, we explored ACR-23 from a pharmacological, physiological, and molecular perspective. Locomotion assays of adult worm showed that BE significantly increased motility. This effect was not observed in acr-23 mutants, indicating that BE acts through ACR-23. MNP decreased worm motility in the adult stage in a concentration-dependent manner with an EC50 of about 30 μM. The acr-23 mutant showed different MNP sensitivity compared to the wild-type strain, indicating that, in addition to ACR-23, other receptors may be targeted by MNP. By using a primary culture of C. elegans muscle cells, we described for the first time the properties of BE-elicited single-channel currents. Opening events showed a mean duration of 0.3 ms and amplitude of about 2.4 pA at a holding potential of 100 mV. The identification and functional characterization of receptors for BE and MNP provides insights into the molecular basis of anthelmintic action, which pave the way for anthelmintic drug design.
Fil: Turani, Ornella. 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: Hernando, Guillermina Silvana. 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
XLIX Reunión Anual de la Sociedad Argentina de Biofísica
Buenos Aires
Argentina
Sociedad Argentina de Biofísica
Materia
NEMATODE
BETAINE
ANTHELMINTIC DRUG
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:11336/229974
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugsTurani, OrnellaHernando, Guillermina SilvanaBouzat, Cecilia BeatrizNEMATODEBETAINEANTHELMINTIC DRUGhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The free-living nematode Caenorhabditis elegans is a model of parasitic nematodes. This worm has the most extensive family of Cys-loop receptors, which are pentameric ligand- gated ion channels that include nicotinic receptors (nAChRs). C. elegans contains an extended family of nAChRs but the functional properties and roles of many of these nAChRs remain unknown. ACR-23 is a nAChR present in neuronal and muscle cells of nematodes and is not conserved in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), a new anthelmintic drug. Given the limited information about its functional role in nematodes, we explored ACR-23 from a pharmacological, physiological, and molecular perspective. Locomotion assays of adult worm showed that BE significantly increased motility. This effect was not observed in acr-23 mutants, indicating that BE acts through ACR-23. MNP decreased worm motility in the adult stage in a concentration-dependent manner with an EC50 of about 30 μM. The acr-23 mutant showed different MNP sensitivity compared to the wild-type strain, indicating that, in addition to ACR-23, other receptors may be targeted by MNP. By using a primary culture of C. elegans muscle cells, we described for the first time the properties of BE-elicited single-channel currents. Opening events showed a mean duration of 0.3 ms and amplitude of about 2.4 pA at a holding potential of 100 mV. The identification and functional characterization of receptors for BE and MNP provides insights into the molecular basis of anthelmintic action, which pave the way for anthelmintic drug design.Fil: Turani, Ornella. 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: Hernando, Guillermina Silvana. 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; ArgentinaXLIX Reunión Anual de la Sociedad Argentina de BiofísicaBuenos AiresArgentinaSociedad Argentina de BiofísicaSociedad Argentina de BiofísicaDelfino, Jose Maria2021info: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/11336/229974Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs; XLIX Reunión Anual de la Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2021; 77-77978-987-27591-9-3CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/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 Técnicas2025-09-03T09:50:16Zoai:ri.conicet.gov.ar:11336/229974instacron: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 09:50:17.085CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs
title Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs
spellingShingle Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs
Turani, Ornella
NEMATODE
BETAINE
ANTHELMINTIC DRUG
title_short Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs
title_full Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs
title_fullStr Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs
title_full_unstemmed Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs
title_sort Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs
dc.creator.none.fl_str_mv Turani, Ornella
Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author Turani, Ornella
author_facet Turani, Ornella
Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author_role author
author2 Hernando, Guillermina Silvana
Bouzat, Cecilia Beatriz
author2_role author
author
dc.contributor.none.fl_str_mv Delfino, Jose Maria
dc.subject.none.fl_str_mv NEMATODE
BETAINE
ANTHELMINTIC DRUG
topic NEMATODE
BETAINE
ANTHELMINTIC DRUG
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 free-living nematode Caenorhabditis elegans is a model of parasitic nematodes. This worm has the most extensive family of Cys-loop receptors, which are pentameric ligand- gated ion channels that include nicotinic receptors (nAChRs). C. elegans contains an extended family of nAChRs but the functional properties and roles of many of these nAChRs remain unknown. ACR-23 is a nAChR present in neuronal and muscle cells of nematodes and is not conserved in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), a new anthelmintic drug. Given the limited information about its functional role in nematodes, we explored ACR-23 from a pharmacological, physiological, and molecular perspective. Locomotion assays of adult worm showed that BE significantly increased motility. This effect was not observed in acr-23 mutants, indicating that BE acts through ACR-23. MNP decreased worm motility in the adult stage in a concentration-dependent manner with an EC50 of about 30 μM. The acr-23 mutant showed different MNP sensitivity compared to the wild-type strain, indicating that, in addition to ACR-23, other receptors may be targeted by MNP. By using a primary culture of C. elegans muscle cells, we described for the first time the properties of BE-elicited single-channel currents. Opening events showed a mean duration of 0.3 ms and amplitude of about 2.4 pA at a holding potential of 100 mV. The identification and functional characterization of receptors for BE and MNP provides insights into the molecular basis of anthelmintic action, which pave the way for anthelmintic drug design.
Fil: Turani, Ornella. 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: Hernando, Guillermina Silvana. 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
XLIX Reunión Anual de la Sociedad Argentina de Biofísica
Buenos Aires
Argentina
Sociedad Argentina de Biofísica
description The free-living nematode Caenorhabditis elegans is a model of parasitic nematodes. This worm has the most extensive family of Cys-loop receptors, which are pentameric ligand- gated ion channels that include nicotinic receptors (nAChRs). C. elegans contains an extended family of nAChRs but the functional properties and roles of many of these nAChRs remain unknown. ACR-23 is a nAChR present in neuronal and muscle cells of nematodes and is not conserved in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), a new anthelmintic drug. Given the limited information about its functional role in nematodes, we explored ACR-23 from a pharmacological, physiological, and molecular perspective. Locomotion assays of adult worm showed that BE significantly increased motility. This effect was not observed in acr-23 mutants, indicating that BE acts through ACR-23. MNP decreased worm motility in the adult stage in a concentration-dependent manner with an EC50 of about 30 μM. The acr-23 mutant showed different MNP sensitivity compared to the wild-type strain, indicating that, in addition to ACR-23, other receptors may be targeted by MNP. By using a primary culture of C. elegans muscle cells, we described for the first time the properties of BE-elicited single-channel currents. Opening events showed a mean duration of 0.3 ms and amplitude of about 2.4 pA at a holding potential of 100 mV. The identification and functional characterization of receptors for BE and MNP provides insights into the molecular basis of anthelmintic action, which pave the way for anthelmintic drug design.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/11336/229974
Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs; XLIX Reunión Anual de la Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2021; 77-77
978-987-27591-9-3
CONICET Digital
CONICET
url http://hdl.handle.net/11336/229974
identifier_str_mv Unravelling the physiological and molecular function of the betaine-sensitive receptor in Caenorhabditis elegans: a new target for anthelmintic drugs; XLIX Reunión Anual de la Sociedad Argentina de Biofísica; Buenos Aires; Argentina; 2021; 77-77
978-987-27591-9-3
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://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/
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 Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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