Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans

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. It has one of the most extensive nicotinic receptor (nAChR) families. However, the molecular functional properties and roles of many of these nAChRs remained unknown. ACR-23 is a nAChR present in neuronal and muscle cells of nematodes and it is not conserved in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), a novel anthelmintic drug. Given the limited information about its functional role in nematodes, we explored ACR-23 from a physiological and molecular perspective. Locomotion assays of adult worm showed that BE significantly increased their motility. This effect was not observed in acr-23 mutants, indicating that BE acts through ACR-23. Interestingly, BE did not affect L1, indicating differential sensitivity between stages, probably arising from changes in ACR-23 expression levels during development. MNP decreased worm motility in the adult stage in a concentration-dependent manner with an EC50 of ~30 µM. The acr-23 mutant showed different MNP sensitivity compared to the wild-type strain, indicating that besides 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. Our study provides insights into the molecular basis of anthelmintic action, which pave the way for the development of novel drugs.
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
XXXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias
Reunión Virtual
Argentina
Sociedad Argentina de Investigación en Neurociencias
Materia
NEMATODES
NICOTINIC RECEPTORS
BETAINE
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:11336/201891
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/201891
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegansTurani, OrnellaHernando, Guillermina SilvanaBouzat, Cecilia BeatrizNEMATODESNICOTINIC RECEPTORSBETAINEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The free-living nematode Caenorhabditis elegans is a model of parasitic nematodes. It has one of the most extensive nicotinic receptor (nAChR) families. However, the molecular functional properties and roles of many of these nAChRs remained unknown. ACR-23 is a nAChR present in neuronal and muscle cells of nematodes and it is not conserved in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), a novel anthelmintic drug. Given the limited information about its functional role in nematodes, we explored ACR-23 from a physiological and molecular perspective. Locomotion assays of adult worm showed that BE significantly increased their motility. This effect was not observed in acr-23 mutants, indicating that BE acts through ACR-23. Interestingly, BE did not affect L1, indicating differential sensitivity between stages, probably arising from changes in ACR-23 expression levels during development. MNP decreased worm motility in the adult stage in a concentration-dependent manner with an EC50 of ~30 µM. The acr-23 mutant showed different MNP sensitivity compared to the wild-type strain, indicating that besides 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. Our study provides insights into the molecular basis of anthelmintic action, which pave the way for the development of novel drugs.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; ArgentinaXXXVI Reunión Anual de la Sociedad Argentina de Investigación en NeurocienciasReunión VirtualArgentinaSociedad Argentina de Investigación en NeurocienciasSociedad Argentina de Investigación en Neurociencias2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfhttp://hdl.handle.net/11336/201891Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans; XXXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; Reunión Virtual; Argentina; 2021; 226-226CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://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 Técnicas2025-09-29T10:46:54Zoai:ri.conicet.gov.ar:11336/201891instacron: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:34982025-09-29 10:46:54.493CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans
title Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans
spellingShingle Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans
Turani, Ornella
NEMATODES
NICOTINIC RECEPTORS
BETAINE
title_short Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans
title_full Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans
title_fullStr Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans
title_full_unstemmed Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans
title_sort Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans
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.subject.none.fl_str_mv NEMATODES
NICOTINIC RECEPTORS
BETAINE
topic NEMATODES
NICOTINIC RECEPTORS
BETAINE
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. It has one of the most extensive nicotinic receptor (nAChR) families. However, the molecular functional properties and roles of many of these nAChRs remained unknown. ACR-23 is a nAChR present in neuronal and muscle cells of nematodes and it is not conserved in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), a novel anthelmintic drug. Given the limited information about its functional role in nematodes, we explored ACR-23 from a physiological and molecular perspective. Locomotion assays of adult worm showed that BE significantly increased their motility. This effect was not observed in acr-23 mutants, indicating that BE acts through ACR-23. Interestingly, BE did not affect L1, indicating differential sensitivity between stages, probably arising from changes in ACR-23 expression levels during development. MNP decreased worm motility in the adult stage in a concentration-dependent manner with an EC50 of ~30 µM. The acr-23 mutant showed different MNP sensitivity compared to the wild-type strain, indicating that besides 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. Our study provides insights into the molecular basis of anthelmintic action, which pave the way for the development of novel drugs.
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
XXXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias
Reunión Virtual
Argentina
Sociedad Argentina de Investigación en Neurociencias
description The free-living nematode Caenorhabditis elegans is a model of parasitic nematodes. It has one of the most extensive nicotinic receptor (nAChR) families. However, the molecular functional properties and roles of many of these nAChRs remained unknown. ACR-23 is a nAChR present in neuronal and muscle cells of nematodes and it is not conserved in vertebrates. It is a cation-selective channel activated by betaine (BE) and sensitive to monepantel (MNP), a novel anthelmintic drug. Given the limited information about its functional role in nematodes, we explored ACR-23 from a physiological and molecular perspective. Locomotion assays of adult worm showed that BE significantly increased their motility. This effect was not observed in acr-23 mutants, indicating that BE acts through ACR-23. Interestingly, BE did not affect L1, indicating differential sensitivity between stages, probably arising from changes in ACR-23 expression levels during development. MNP decreased worm motility in the adult stage in a concentration-dependent manner with an EC50 of ~30 µM. The acr-23 mutant showed different MNP sensitivity compared to the wild-type strain, indicating that besides 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. Our study provides insights into the molecular basis of anthelmintic action, which pave the way for the development of novel drugs.
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
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/11336/201891
Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans; XXXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; Reunión Virtual; Argentina; 2021; 226-226
CONICET Digital
CONICET
url http://hdl.handle.net/11336/201891
identifier_str_mv Unravelling the physiological role and molecular function of betaine-sensitive nicotinic receptors of Caenorhabditis elegans; XXXVI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; Reunión Virtual; Argentina; 2021; 226-226
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/
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/vnd.openxmlformats-officedocument.wordprocessingml.document
application/vnd.openxmlformats-officedocument.wordprocessingml.document
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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score 13.070432

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