Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter

Autores
Di Scala, Coralie; Fantini, Jacques; Yahi, Nouara; Barrantes, Francisco José; Chahinian, Henri
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Di Scala, Coralie. Institut de neurobiologie de la méditerranée; Francia
Fil: Fantini, Jacques. Aix-Marseille Université; Francia
Fil: Yahi, Nouara. Aix-Marseille Université; Francia
Fil: Barrantes, Francisco J. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neurbiología Molecular; Argentina
Fil: Barrantes, Francisco J. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chahinian, Henri. Aix-Marseille Université; Francia
Abstract: Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid. The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid. In this review, we first analyze the conformational flexibility of anandamide in aqueous and membrane phases. We next study the interaction of the neurotransmitter with membrane lipids and discuss the molecular basis of the unexpected selectivity of anandamide for cholesterol and ceramide from among other membrane lipids. We show that cholesterol behaves as a binding partner for anandamide, and that following an initial interaction mediated by the establishment of a hydrogen bond, anandamide is attracted towards the membrane interior, where it forms a molecular complex with cholesterol after a functional conformation adaptation to the apolar membrane milieu. The complex is then directed to the anandamide cannabinoid receptor (CB1) which displays a high affinity binding pocket for anandamide. We propose that cholesterol may regulate the entry and exit of anandamide in and out of CB1 by interacting with low affinity cholesterol recognition sites (CARC and CRAC) located in transmembrane helices. The mirror topology of cholesterol binding sites in the seventh transmembrane domain is consistent with the delivery, extraction and flip-flop of anandamide through a coordinated cholesterol-dependent mechanism. The binding of anandamide to ceramide illustrates another key function of membrane lipids which may occur independently of protein receptors. Interestingly, ceramide forms a tight complex with anandamide which blocks the degradation pathway of both lipids and could be exploited for anti-cancer therapies.
Fuente
Biomolecules. 2018, 8 (2)
Materia
COLESTEROL
ANANDAMIDA
CERAMIDA
LIPIDOS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
Repositorio Institucional (UCA)
Institución
Pontificia Universidad Católica Argentina
OAI Identificador
oai:ucacris:123456789/1444

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oai_identifier_str oai:ucacris:123456789/1444
network_acronym_str RIUCA
repository_id_str 2585
network_name_str Repositorio Institucional (UCA)
spelling Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitterDi Scala, CoralieFantini, JacquesYahi, NouaraBarrantes, Francisco JoséChahinian, HenriCOLESTEROLANANDAMIDACERAMIDALIPIDOSFil: Di Scala, Coralie. Institut de neurobiologie de la méditerranée; FranciaFil: Fantini, Jacques. Aix-Marseille Université; FranciaFil: Yahi, Nouara. Aix-Marseille Université; FranciaFil: Barrantes, Francisco J. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neurbiología Molecular; ArgentinaFil: Barrantes, Francisco J. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chahinian, Henri. Aix-Marseille Université; FranciaAbstract: Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid. The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid. In this review, we first analyze the conformational flexibility of anandamide in aqueous and membrane phases. We next study the interaction of the neurotransmitter with membrane lipids and discuss the molecular basis of the unexpected selectivity of anandamide for cholesterol and ceramide from among other membrane lipids. We show that cholesterol behaves as a binding partner for anandamide, and that following an initial interaction mediated by the establishment of a hydrogen bond, anandamide is attracted towards the membrane interior, where it forms a molecular complex with cholesterol after a functional conformation adaptation to the apolar membrane milieu. The complex is then directed to the anandamide cannabinoid receptor (CB1) which displays a high affinity binding pocket for anandamide. We propose that cholesterol may regulate the entry and exit of anandamide in and out of CB1 by interacting with low affinity cholesterol recognition sites (CARC and CRAC) located in transmembrane helices. The mirror topology of cholesterol binding sites in the seventh transmembrane domain is consistent with the delivery, extraction and flip-flop of anandamide through a coordinated cholesterol-dependent mechanism. The binding of anandamide to ceramide illustrates another key function of membrane lipids which may occur independently of protein receptors. Interestingly, ceramide forms a tight complex with anandamide which blocks the degradation pathway of both lipids and could be exploited for anti-cancer therapies.MDPI2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttps://repositorio.uca.edu.ar/handle/123456789/14442218-273X (online)10.3390/biom8020031Di Scala, C., et al. Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter [en línea]. Biomolecules. 2018, 8 (2). doi:10.3390/biom8020031. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/1444Biomolecules. 2018, 8 (2)reponame:Repositorio Institucional (UCA)instname:Pontificia Universidad Católica Argentinaengenginfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/4.0/2025-07-03T10:55:17Zoai:ucacris:123456789/1444instacron:UCAInstitucionalhttps://repositorio.uca.edu.ar/Universidad privadaNo correspondehttps://repositorio.uca.edu.ar/oaiclaudia_fernandez@uca.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:25852025-07-03 10:55:17.884Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentinafalse
dc.title.none.fl_str_mv Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter
title Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter
spellingShingle Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter
Di Scala, Coralie
COLESTEROL
ANANDAMIDA
CERAMIDA
LIPIDOS
title_short Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter
title_full Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter
title_fullStr Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter
title_full_unstemmed Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter
title_sort Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter
dc.creator.none.fl_str_mv Di Scala, Coralie
Fantini, Jacques
Yahi, Nouara
Barrantes, Francisco José
Chahinian, Henri
author Di Scala, Coralie
author_facet Di Scala, Coralie
Fantini, Jacques
Yahi, Nouara
Barrantes, Francisco José
Chahinian, Henri
author_role author
author2 Fantini, Jacques
Yahi, Nouara
Barrantes, Francisco José
Chahinian, Henri
author2_role author
author
author
author
dc.subject.none.fl_str_mv COLESTEROL
ANANDAMIDA
CERAMIDA
LIPIDOS
topic COLESTEROL
ANANDAMIDA
CERAMIDA
LIPIDOS
dc.description.none.fl_txt_mv Fil: Di Scala, Coralie. Institut de neurobiologie de la méditerranée; Francia
Fil: Fantini, Jacques. Aix-Marseille Université; Francia
Fil: Yahi, Nouara. Aix-Marseille Université; Francia
Fil: Barrantes, Francisco J. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas. Laboratorio de Neurbiología Molecular; Argentina
Fil: Barrantes, Francisco J. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chahinian, Henri. Aix-Marseille Université; Francia
Abstract: Anandamide is a lipid neurotransmitter derived from arachidonic acid, a polyunsaturated fatty acid. The chemical differences between anandamide and arachidonic acid result in a slightly enhanced solubility in water and absence of an ionisable group for the neurotransmitter compared with the fatty acid. In this review, we first analyze the conformational flexibility of anandamide in aqueous and membrane phases. We next study the interaction of the neurotransmitter with membrane lipids and discuss the molecular basis of the unexpected selectivity of anandamide for cholesterol and ceramide from among other membrane lipids. We show that cholesterol behaves as a binding partner for anandamide, and that following an initial interaction mediated by the establishment of a hydrogen bond, anandamide is attracted towards the membrane interior, where it forms a molecular complex with cholesterol after a functional conformation adaptation to the apolar membrane milieu. The complex is then directed to the anandamide cannabinoid receptor (CB1) which displays a high affinity binding pocket for anandamide. We propose that cholesterol may regulate the entry and exit of anandamide in and out of CB1 by interacting with low affinity cholesterol recognition sites (CARC and CRAC) located in transmembrane helices. The mirror topology of cholesterol binding sites in the seventh transmembrane domain is consistent with the delivery, extraction and flip-flop of anandamide through a coordinated cholesterol-dependent mechanism. The binding of anandamide to ceramide illustrates another key function of membrane lipids which may occur independently of protein receptors. Interestingly, ceramide forms a tight complex with anandamide which blocks the degradation pathway of both lipids and could be exploited for anti-cancer therapies.
description Fil: Di Scala, Coralie. Institut de neurobiologie de la méditerranée; Francia
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://repositorio.uca.edu.ar/handle/123456789/1444
2218-273X (online)
10.3390/biom8020031
Di Scala, C., et al. Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter [en línea]. Biomolecules. 2018, 8 (2). doi:10.3390/biom8020031. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/1444
url https://repositorio.uca.edu.ar/handle/123456789/1444
identifier_str_mv 2218-273X (online)
10.3390/biom8020031
Di Scala, C., et al. Anandamide revisited : how cholesterol and ceramides control receptor-dependent and receptor-independent signal transmission pathways of a lipid neurotransmitter [en línea]. Biomolecules. 2018, 8 (2). doi:10.3390/biom8020031. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/1444
dc.language.none.fl_str_mv eng
eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Biomolecules. 2018, 8 (2)
reponame:Repositorio Institucional (UCA)
instname:Pontificia Universidad Católica Argentina
reponame_str Repositorio Institucional (UCA)
collection Repositorio Institucional (UCA)
instname_str Pontificia Universidad Católica Argentina
repository.name.fl_str_mv Repositorio Institucional (UCA) - Pontificia Universidad Católica Argentina
repository.mail.fl_str_mv claudia_fernandez@uca.edu.ar
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score 13.070432