Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation

Autores
Toneatto, Judith; Guber, Sergio; Charó, Nancy Lorena; Susperreguy, Sebastian; Schwartz, Jessica; Galigniana, Mario Daniel; Piwien Pilipuk, Graciela
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Glucocorticoids play an important role in adipogenesis via the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90•Hsp70 and one high molecular weight immunophilin FKBP51 or FKBP52. When 3T3-L1 preadipocytes are induced to differentiate, FKBP51 expression progressively increases, whereas FKBP52 decreases, and Hsp90, Hsp70, p23 and Cyp40 remain unchanged. Interestingly, FKBP51 rapidly translocates from mitochondria to the nucleus where it is retained upon its interaction with chromatin and the nuclear matrix. FKBP51 nuclear localization is transient, after 48 h it cycles back to mitochondria. Importantly, this dynamic FKBP51 mitochondrial-nuclear shuttling depends on PKA signaling, since its inhibition by PKI or knock-down of PKA-cα by siRNA, abrogated FKBP51 nuclear translocation induced by IBMX. In addition, FKBP51 electrophoretic pattern of migration is altered by treatment of cells with PKI or knock-down of PKA-cα suggesting that FKBP51 is a PKA substrate. In preadipocytes, FKBP51 co-localizes with PKA-cα in mitochondria. When adipogenesis is triggered, PKA-cα also moves to the nucleus co-localizing with FKBP51 mainly in the nuclear lamina. Moreover, FKBP51 and GR interaction increases when preadipocytes are induced to differentiate. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutiryl-cAMP, compounds that induced FKBP51 nuclear translocation, but not by an specific activator of EPAC. FKBP51 knock-down facilitates while ectopic expression of FKBP51 blocks adipogenesis. These findings indicate that the dynamic mitochondrial-nuclear shuttling of FKBP51 regulated by PKA may be key in fine tuning the transcriptional control of GR-target genes required for the acquisition of adipocyte phenotype.
Fil: Toneatto, Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Guber, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Charó, Nancy Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Susperreguy, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Schwartz, Jessica. University Of Michigan; Estados Unidos
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Piwien Pilipuk, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
FKBP51
RECEPTOR DE GLUCOCORTICOIDES
ADIPOGENESIS
PKA
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:11336/5355
Acceder
id CONICETDig_02c6e55804a030678c6e86be0399f6fe
oai_identifier_str oai:ri.conicet.gov.ar:11336/5355
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiationToneatto, JudithGuber, SergioCharó, Nancy LorenaSusperreguy, SebastianSchwartz, JessicaGaligniana, Mario DanielPiwien Pilipuk, GracielaFKBP51RECEPTOR DE GLUCOCORTICOIDESADIPOGENESISPKAhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Glucocorticoids play an important role in adipogenesis via the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90•Hsp70 and one high molecular weight immunophilin FKBP51 or FKBP52. When 3T3-L1 preadipocytes are induced to differentiate, FKBP51 expression progressively increases, whereas FKBP52 decreases, and Hsp90, Hsp70, p23 and Cyp40 remain unchanged. Interestingly, FKBP51 rapidly translocates from mitochondria to the nucleus where it is retained upon its interaction with chromatin and the nuclear matrix. FKBP51 nuclear localization is transient, after 48 h it cycles back to mitochondria. Importantly, this dynamic FKBP51 mitochondrial-nuclear shuttling depends on PKA signaling, since its inhibition by PKI or knock-down of PKA-cα by siRNA, abrogated FKBP51 nuclear translocation induced by IBMX. In addition, FKBP51 electrophoretic pattern of migration is altered by treatment of cells with PKI or knock-down of PKA-cα suggesting that FKBP51 is a PKA substrate. In preadipocytes, FKBP51 co-localizes with PKA-cα in mitochondria. When adipogenesis is triggered, PKA-cα also moves to the nucleus co-localizing with FKBP51 mainly in the nuclear lamina. Moreover, FKBP51 and GR interaction increases when preadipocytes are induced to differentiate. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutiryl-cAMP, compounds that induced FKBP51 nuclear translocation, but not by an specific activator of EPAC. FKBP51 knock-down facilitates while ectopic expression of FKBP51 blocks adipogenesis. These findings indicate that the dynamic mitochondrial-nuclear shuttling of FKBP51 regulated by PKA may be key in fine tuning the transcriptional control of GR-target genes required for the acquisition of adipocyte phenotype.Fil: Toneatto, Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Guber, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; ArgentinaFil: Charó, Nancy Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Susperreguy, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Schwartz, Jessica. University Of Michigan; Estados UnidosFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Piwien Pilipuk, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaCompany of Biologists2013-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/5355Toneatto, Judith; Guber, Sergio; Charó, Nancy Lorena; Susperreguy, Sebastian; Schwartz, Jessica; et al.; Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation; Company of Biologists; Journal of Cell Science; 126; 12-2013; 5357-53680021-95331477-9137enginfo:eu-repo/semantics/altIdentifier/url/http://jcs.biologists.org/content/126/23/5357info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/pmid/PMC3843136info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843136/info:eu-repo/semantics/altIdentifier/url/http://doi.org/10.1242/jcs.125799info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:18:40Zoai:ri.conicet.gov.ar:11336/5355instacron: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 10:18:41.194CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
title Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
spellingShingle Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
Toneatto, Judith
FKBP51
RECEPTOR DE GLUCOCORTICOIDES
ADIPOGENESIS
PKA
title_short Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
title_full Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
title_fullStr Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
title_full_unstemmed Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
title_sort Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
dc.creator.none.fl_str_mv Toneatto, Judith
Guber, Sergio
Charó, Nancy Lorena
Susperreguy, Sebastian
Schwartz, Jessica
Galigniana, Mario Daniel
Piwien Pilipuk, Graciela
author Toneatto, Judith
author_facet Toneatto, Judith
Guber, Sergio
Charó, Nancy Lorena
Susperreguy, Sebastian
Schwartz, Jessica
Galigniana, Mario Daniel
Piwien Pilipuk, Graciela
author_role author
author2 Guber, Sergio
Charó, Nancy Lorena
Susperreguy, Sebastian
Schwartz, Jessica
Galigniana, Mario Daniel
Piwien Pilipuk, Graciela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv FKBP51
RECEPTOR DE GLUCOCORTICOIDES
ADIPOGENESIS
PKA
topic FKBP51
RECEPTOR DE GLUCOCORTICOIDES
ADIPOGENESIS
PKA
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Glucocorticoids play an important role in adipogenesis via the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90•Hsp70 and one high molecular weight immunophilin FKBP51 or FKBP52. When 3T3-L1 preadipocytes are induced to differentiate, FKBP51 expression progressively increases, whereas FKBP52 decreases, and Hsp90, Hsp70, p23 and Cyp40 remain unchanged. Interestingly, FKBP51 rapidly translocates from mitochondria to the nucleus where it is retained upon its interaction with chromatin and the nuclear matrix. FKBP51 nuclear localization is transient, after 48 h it cycles back to mitochondria. Importantly, this dynamic FKBP51 mitochondrial-nuclear shuttling depends on PKA signaling, since its inhibition by PKI or knock-down of PKA-cα by siRNA, abrogated FKBP51 nuclear translocation induced by IBMX. In addition, FKBP51 electrophoretic pattern of migration is altered by treatment of cells with PKI or knock-down of PKA-cα suggesting that FKBP51 is a PKA substrate. In preadipocytes, FKBP51 co-localizes with PKA-cα in mitochondria. When adipogenesis is triggered, PKA-cα also moves to the nucleus co-localizing with FKBP51 mainly in the nuclear lamina. Moreover, FKBP51 and GR interaction increases when preadipocytes are induced to differentiate. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutiryl-cAMP, compounds that induced FKBP51 nuclear translocation, but not by an specific activator of EPAC. FKBP51 knock-down facilitates while ectopic expression of FKBP51 blocks adipogenesis. These findings indicate that the dynamic mitochondrial-nuclear shuttling of FKBP51 regulated by PKA may be key in fine tuning the transcriptional control of GR-target genes required for the acquisition of adipocyte phenotype.
Fil: Toneatto, Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Guber, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
Fil: Charó, Nancy Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Susperreguy, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Schwartz, Jessica. University Of Michigan; Estados Unidos
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Piwien Pilipuk, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description Glucocorticoids play an important role in adipogenesis via the glucocorticoid receptor (GR) that forms a heterocomplex with Hsp90•Hsp70 and one high molecular weight immunophilin FKBP51 or FKBP52. When 3T3-L1 preadipocytes are induced to differentiate, FKBP51 expression progressively increases, whereas FKBP52 decreases, and Hsp90, Hsp70, p23 and Cyp40 remain unchanged. Interestingly, FKBP51 rapidly translocates from mitochondria to the nucleus where it is retained upon its interaction with chromatin and the nuclear matrix. FKBP51 nuclear localization is transient, after 48 h it cycles back to mitochondria. Importantly, this dynamic FKBP51 mitochondrial-nuclear shuttling depends on PKA signaling, since its inhibition by PKI or knock-down of PKA-cα by siRNA, abrogated FKBP51 nuclear translocation induced by IBMX. In addition, FKBP51 electrophoretic pattern of migration is altered by treatment of cells with PKI or knock-down of PKA-cα suggesting that FKBP51 is a PKA substrate. In preadipocytes, FKBP51 co-localizes with PKA-cα in mitochondria. When adipogenesis is triggered, PKA-cα also moves to the nucleus co-localizing with FKBP51 mainly in the nuclear lamina. Moreover, FKBP51 and GR interaction increases when preadipocytes are induced to differentiate. GR transcriptional capacity is reduced when cells are incubated in the presence of IBMX, forskolin or dibutiryl-cAMP, compounds that induced FKBP51 nuclear translocation, but not by an specific activator of EPAC. FKBP51 knock-down facilitates while ectopic expression of FKBP51 blocks adipogenesis. These findings indicate that the dynamic mitochondrial-nuclear shuttling of FKBP51 regulated by PKA may be key in fine tuning the transcriptional control of GR-target genes required for the acquisition of adipocyte phenotype.
publishDate 2013
dc.date.none.fl_str_mv 2013-12
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/11336/5355
Toneatto, Judith; Guber, Sergio; Charó, Nancy Lorena; Susperreguy, Sebastian; Schwartz, Jessica; et al.; Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation; Company of Biologists; Journal of Cell Science; 126; 12-2013; 5357-5368
0021-9533
1477-9137
url http://hdl.handle.net/11336/5355
identifier_str_mv Toneatto, Judith; Guber, Sergio; Charó, Nancy Lorena; Susperreguy, Sebastian; Schwartz, Jessica; et al.; Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation; Company of Biologists; Journal of Cell Science; 126; 12-2013; 5357-5368
0021-9533
1477-9137
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://jcs.biologists.org/content/126/23/5357
info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/pmid/PMC3843136
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843136/
info:eu-repo/semantics/altIdentifier/url/http://doi.org/10.1242/jcs.125799
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
dc.publisher.none.fl_str_mv Company of Biologists
publisher.none.fl_str_mv Company of Biologists
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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