INVESTIGADORES
GALIGNIANA Mario Daniel
congresos y reuniones científicas
Título:
Dynamic mitochondrial-nuclear redistribution of the immunophilin FKBP51 is regulated by PKA signalling pathway in the process of adipocyte differentiation
Autor/es:
TONEATTO J, CHARó N, GALIGNIANA MD, PIWIEN PILIPUK G
Lugar:
Les Diablerets
Reunión:
Congreso; The 6 th. International Conference on the Hsp90-Chaperone Machine; 2012
Resumen:
Glucocorticoids play an important role in adipogenesis
via the glucocorticoid receptor (GR)
that forms a heterocomplex with Hsp90-Hsp70 and a high molecular weight
immunophilin FKBP51 or FKBP52. When 3T3-L1 preadipocytes are induced to
differentiate, FKBP51 level progressively increases, FKBP52 decreases, whereas
Hsp90, Hsp70, p23 and Cyp40 remain unchanged, as shown by Western blot.
Interestingly, when adipogenesis is induced, FKBP51 translocates from
mitochondria to the nucleus. FKBP51 is retained
in the nucleus upon its interaction with chromatin and the nuclear matrix.
FKBP51 nuclear localization is transient, after 48 h it cycles back to
mitochondria. Importantly, the dynamic FKBP51 mitochondrial-nuclear shuttling
depends on PKA signaling, since its inhibition by PKI or knock down of PKA-cá by siRNA, abrogated FKBP51 nuclear translocation
induced by IBMX. In addition, the electrophoretic pattern of migration of
FKBP51 is altered by treatment of cells with PKI or knock-down of PKA-cá suggesting that FKBP51 is a PKA substrate. In
preadipocytes, FKBP51 co-localizes with PKA-cá in mitochondria. When adipogenesis is triggered PKA also moves to the
nucleus co-localizing with FKBP51. 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 nuclear translocation of FKBP51, but
not by an specific activator of EPAC. These findings raise the possibility 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.