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dc.contributor.author
Toneatto, Judith
dc.contributor.author
Guber, Sergio
dc.contributor.author
Charó, Nancy Lorena
dc.contributor.author
Susperreguy, Sebastian
dc.contributor.author
Schwartz, Jessica
dc.contributor.author
Galigniana, Mario Daniel
dc.contributor.author
Piwien Pilipuk, Graciela
dc.date.available
2016-04-25T14:32:34Z
dc.date.issued
2013-12
dc.identifier.citation
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
dc.identifier.issn
0021-9533
dc.identifier.uri
http://hdl.handle.net/11336/5355
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Company of Biologists
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Fkbp51
dc.subject
Receptor de Glucocorticoides
dc.subject
Adipogenesis
dc.subject
Pka
dc.subject.classification
Biología Celular, Microbiología
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Dynamic mitochondrial–nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-05-06 15:52:43.262787-03
dc.identifier.eissn
1477-9137
dc.journal.volume
126
dc.journal.pagination
5357-5368
dc.journal.pais
Reino Unido
dc.journal.ciudad
Cambridge
dc.description.fil
Fil: Toneatto, Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
dc.description.fil
Fil: Guber, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina
dc.description.fil
Fil: Charó, Nancy Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
dc.description.fil
Fil: Susperreguy, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
dc.description.fil
Fil: Schwartz, Jessica. University Of Michigan; Estados Unidos
dc.description.fil
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
dc.description.fil
Fil: Piwien Pilipuk, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
dc.journal.title
Journal of Cell Science
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://jcs.biologists.org/content/126/23/5357
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/10.1242/jcs.125799
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/pmid/PMC3843136
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843136/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://doi.org/10.1242/jcs.125799


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