Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate

Autores
Lopez, Cecilia Ines; Pelletán, Leonardo Enuar; Suhaiman, Laila; de Blas, Gerardo Andrés; Vitale, Nicolas; Mayorga, Luis Segundo; Belmonte, Silvia Alejandra
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Acrosomal exocytosis involves a massive fusion between the outer acrosomal and the plasma membranes of the spermatozoon triggered by stimuli that open calcium channels at the plasma membrane. Diacylglycerol has been implicated in the activation of these calcium channels. Here we report that this lipid promotes the efflux of intraacrosomal calcium and triggers exocytosis in permeabilized human sperm, implying that diacylglycerol activates events downstream of the opening of plasma membrane channels. Furthermore, we show that calcium and diacylglycerol converge in a signaling pathway leading to the production of phosphatidylinositol 4,5-bisphosphate (PIP2). Addition of diacylglycerol promotes the PKC-dependent activation of PLD1. Rescue experiments adding phosphatidic acid or PIP2 and direct measurement of lipid production suggest that both PKC and PLD1 promote PIP2 synthesis. Inhibition of different steps of the pathway was reverted by adenophostin, an agonist of IP3-sensitive calcium channels, indicating that PIP2 is necessary to keep these channels opened. However, phosphatidic acid, PIP2, or adenophostin could not trigger exocytosis by themselves, indicating that diacylglycerol must also activate another factor. We found that diacylglycerol and phorbol ester stimulate the accumulation of the GTP-bound form of Rab3A. Together our results indicate that diacylglycerol promotes acrosomal exocytosis by i) maintaining high levels of IP3 – an effect that depends on a positive feedback loop leading to the production of PIP2 – and ii) stimulating the activation of Rab3A, which in turn initiates a cascade of protein interactions leading to the assembly of SNARE complexes and membrane fusion.
Fil: Lopez, Cecilia Ines. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Pelletán, Leonardo Enuar. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Suhaiman, Laila. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: de Blas, Gerardo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Vitale, Nicolas. Université de Strasbourg; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Belmonte, Silvia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Materia
ACROSOMAL EXOCYTOSIS
DIACYLGLYCEROL
PHOSPHATIDIC ACID
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE
PHOSPHOLIPASE D
REGULATED EXOCYTOSIS
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:11336/144976
Acceder
id CONICETDig_4df041b29ab9852b28c3cb27646dabbb
oai_identifier_str oai:ri.conicet.gov.ar:11336/144976
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphateLopez, Cecilia InesPelletán, Leonardo EnuarSuhaiman, Lailade Blas, Gerardo AndrésVitale, NicolasMayorga, Luis SegundoBelmonte, Silvia AlejandraACROSOMAL EXOCYTOSISDIACYLGLYCEROLPHOSPHATIDIC ACIDPHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATEPHOSPHOLIPASE DREGULATED EXOCYTOSIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Acrosomal exocytosis involves a massive fusion between the outer acrosomal and the plasma membranes of the spermatozoon triggered by stimuli that open calcium channels at the plasma membrane. Diacylglycerol has been implicated in the activation of these calcium channels. Here we report that this lipid promotes the efflux of intraacrosomal calcium and triggers exocytosis in permeabilized human sperm, implying that diacylglycerol activates events downstream of the opening of plasma membrane channels. Furthermore, we show that calcium and diacylglycerol converge in a signaling pathway leading to the production of phosphatidylinositol 4,5-bisphosphate (PIP2). Addition of diacylglycerol promotes the PKC-dependent activation of PLD1. Rescue experiments adding phosphatidic acid or PIP2 and direct measurement of lipid production suggest that both PKC and PLD1 promote PIP2 synthesis. Inhibition of different steps of the pathway was reverted by adenophostin, an agonist of IP3-sensitive calcium channels, indicating that PIP2 is necessary to keep these channels opened. However, phosphatidic acid, PIP2, or adenophostin could not trigger exocytosis by themselves, indicating that diacylglycerol must also activate another factor. We found that diacylglycerol and phorbol ester stimulate the accumulation of the GTP-bound form of Rab3A. Together our results indicate that diacylglycerol promotes acrosomal exocytosis by i) maintaining high levels of IP3 – an effect that depends on a positive feedback loop leading to the production of PIP2 – and ii) stimulating the activation of Rab3A, which in turn initiates a cascade of protein interactions leading to the assembly of SNARE complexes and membrane fusion.Fil: Lopez, Cecilia Ines. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Pelletán, Leonardo Enuar. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Suhaiman, Laila. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: de Blas, Gerardo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Vitale, Nicolas. Université de Strasbourg; Francia. Centre National de la Recherche Scientifique; FranciaFil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Belmonte, Silvia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaElsevier Science2012-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/144976Lopez, Cecilia Ines; Pelletán, Leonardo Enuar; Suhaiman, Laila; de Blas, Gerardo Andrés; Vitale, Nicolas; et al.; Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate; Elsevier Science; Biochimica Et Biophysica Acta - Molecular and Cell Biology of Lipids; 1821; 9; 9-2012; 1186-11991388-1981CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbalip.2012.05.001info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S138819811200090Xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:18:06Zoai:ri.conicet.gov.ar:11336/144976instacron: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 10:18:07.222CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate
title Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate
spellingShingle Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate
Lopez, Cecilia Ines
ACROSOMAL EXOCYTOSIS
DIACYLGLYCEROL
PHOSPHATIDIC ACID
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE
PHOSPHOLIPASE D
REGULATED EXOCYTOSIS
title_short Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate
title_full Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate
title_fullStr Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate
title_full_unstemmed Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate
title_sort Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate
dc.creator.none.fl_str_mv Lopez, Cecilia Ines
Pelletán, Leonardo Enuar
Suhaiman, Laila
de Blas, Gerardo Andrés
Vitale, Nicolas
Mayorga, Luis Segundo
Belmonte, Silvia Alejandra
author Lopez, Cecilia Ines
author_facet Lopez, Cecilia Ines
Pelletán, Leonardo Enuar
Suhaiman, Laila
de Blas, Gerardo Andrés
Vitale, Nicolas
Mayorga, Luis Segundo
Belmonte, Silvia Alejandra
author_role author
author2 Pelletán, Leonardo Enuar
Suhaiman, Laila
de Blas, Gerardo Andrés
Vitale, Nicolas
Mayorga, Luis Segundo
Belmonte, Silvia Alejandra
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ACROSOMAL EXOCYTOSIS
DIACYLGLYCEROL
PHOSPHATIDIC ACID
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE
PHOSPHOLIPASE D
REGULATED EXOCYTOSIS
topic ACROSOMAL EXOCYTOSIS
DIACYLGLYCEROL
PHOSPHATIDIC ACID
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE
PHOSPHOLIPASE D
REGULATED EXOCYTOSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Acrosomal exocytosis involves a massive fusion between the outer acrosomal and the plasma membranes of the spermatozoon triggered by stimuli that open calcium channels at the plasma membrane. Diacylglycerol has been implicated in the activation of these calcium channels. Here we report that this lipid promotes the efflux of intraacrosomal calcium and triggers exocytosis in permeabilized human sperm, implying that diacylglycerol activates events downstream of the opening of plasma membrane channels. Furthermore, we show that calcium and diacylglycerol converge in a signaling pathway leading to the production of phosphatidylinositol 4,5-bisphosphate (PIP2). Addition of diacylglycerol promotes the PKC-dependent activation of PLD1. Rescue experiments adding phosphatidic acid or PIP2 and direct measurement of lipid production suggest that both PKC and PLD1 promote PIP2 synthesis. Inhibition of different steps of the pathway was reverted by adenophostin, an agonist of IP3-sensitive calcium channels, indicating that PIP2 is necessary to keep these channels opened. However, phosphatidic acid, PIP2, or adenophostin could not trigger exocytosis by themselves, indicating that diacylglycerol must also activate another factor. We found that diacylglycerol and phorbol ester stimulate the accumulation of the GTP-bound form of Rab3A. Together our results indicate that diacylglycerol promotes acrosomal exocytosis by i) maintaining high levels of IP3 – an effect that depends on a positive feedback loop leading to the production of PIP2 – and ii) stimulating the activation of Rab3A, which in turn initiates a cascade of protein interactions leading to the assembly of SNARE complexes and membrane fusion.
Fil: Lopez, Cecilia Ines. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Pelletán, Leonardo Enuar. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Suhaiman, Laila. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: de Blas, Gerardo Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Vitale, Nicolas. Université de Strasbourg; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Belmonte, Silvia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
description Acrosomal exocytosis involves a massive fusion between the outer acrosomal and the plasma membranes of the spermatozoon triggered by stimuli that open calcium channels at the plasma membrane. Diacylglycerol has been implicated in the activation of these calcium channels. Here we report that this lipid promotes the efflux of intraacrosomal calcium and triggers exocytosis in permeabilized human sperm, implying that diacylglycerol activates events downstream of the opening of plasma membrane channels. Furthermore, we show that calcium and diacylglycerol converge in a signaling pathway leading to the production of phosphatidylinositol 4,5-bisphosphate (PIP2). Addition of diacylglycerol promotes the PKC-dependent activation of PLD1. Rescue experiments adding phosphatidic acid or PIP2 and direct measurement of lipid production suggest that both PKC and PLD1 promote PIP2 synthesis. Inhibition of different steps of the pathway was reverted by adenophostin, an agonist of IP3-sensitive calcium channels, indicating that PIP2 is necessary to keep these channels opened. However, phosphatidic acid, PIP2, or adenophostin could not trigger exocytosis by themselves, indicating that diacylglycerol must also activate another factor. We found that diacylglycerol and phorbol ester stimulate the accumulation of the GTP-bound form of Rab3A. Together our results indicate that diacylglycerol promotes acrosomal exocytosis by i) maintaining high levels of IP3 – an effect that depends on a positive feedback loop leading to the production of PIP2 – and ii) stimulating the activation of Rab3A, which in turn initiates a cascade of protein interactions leading to the assembly of SNARE complexes and membrane fusion.
publishDate 2012
dc.date.none.fl_str_mv 2012-09
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 http://hdl.handle.net/11336/144976
Lopez, Cecilia Ines; Pelletán, Leonardo Enuar; Suhaiman, Laila; de Blas, Gerardo Andrés; Vitale, Nicolas; et al.; Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate; Elsevier Science; Biochimica Et Biophysica Acta - Molecular and Cell Biology of Lipids; 1821; 9; 9-2012; 1186-1199
1388-1981
CONICET Digital
CONICET
url http://hdl.handle.net/11336/144976
identifier_str_mv Lopez, Cecilia Ines; Pelletán, Leonardo Enuar; Suhaiman, Laila; de Blas, Gerardo Andrés; Vitale, Nicolas; et al.; Diacylglycerol stimulates acrosomal exocytosis by feeding into a PKC- and PLD1-dependent positive loop that continuously supplies phosphatidylinositol 4,5-bisphosphate; Elsevier Science; Biochimica Et Biophysica Acta - Molecular and Cell Biology of Lipids; 1821; 9; 9-2012; 1186-1199
1388-1981
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbalip.2012.05.001
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S138819811200090X
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.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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