The hsp90•FKBP52 complex links the mineralocorticoid receptor to motor proteins and persists bound to the receptor in early nuclear events

GALIGNIANA MD; ERLEJMAN A; MONTE M; GOMEZ-SANCHEZ C; PIWIEN PILIPUK G

MOLECULAR AND CELLULAR BIOLOGY

AMER SOC MICROBIOLOGY

Año: 2010 vol. 30 p. 1285 - 1298

0270-7306

In this study we demonstrate that the subcellular localization of the mineralocorticoid receptor (MR) is regulated by tetratricopeptide domain (TPR) proteins. The high molecular weight immunophilin (IMM) FKBP52 links the MR•hsp90 complex to dynein/dynactin motors favoring the cytoplasmic transport of MR to the nucleus. Replacement of this hsp90-binding IMM by FKBP51 or the TPR peptide favored the cytoplasmic localization of MR. The complete movement machinery, including dynein and tubulin, could be recovered from paclitaxel/GTP-stabilized cytosol and was fully reassembled on stripped MR immune pellets. The whole MR•hsp90-based heterocomplex was transiently recovered in the soluble fraction of the nucleus after ten minutes of incubation with aldosterone. Moreover, cross-linked MR•hsp90 heterocomplexes accumulated in the nucleus in a hormone-dependent manner, demonstrating that the heterocomplex can pass undissociated through the nuclear pore. On the other hand, a peptide that comprises the DNA-binding domain of MR impaired the nuclear export of MR, suggesting the involvement of this domain in the process. This study represents the first report describing the entire molecular system that commands the MR nucleo-cytoplasmic trafficking, and proposes that the MR•hsp90•TPR protein heterocomplex is dissociated in the nucleus rather than in the cytoplasm.