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
- Institución
- Pontificia Universidad Católica Argentina
- OAI Identificador
- oai:ucacris:123456789/1444
Ver los metadatos del registro completo
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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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1836638330112966656 |
score |
13.070432 |