Figure 2: The GR•Hsp90•FKBP52 Molecular Machinery of Movement. (A) The glucocorticoid receptor (GR) is shown as a standard model. GR is associated to a dimer of Hsp90 and one molecule of Hsp70, p23, and a TPR-domain immunophilin. The inactive isoforms of the heterocomplex are primarily cytoplasmic and FKBP51 is recovered bound to the chaperone complex. Upon steroid binding, FKBP51 is exchanged by FKBP52, a highly homologous IMM that is able to interact with dynein/dynactin motor proteins. This molecular complex retrotransports GR to the nuclear compartment using microtubule tracks. Arrows show the points where the complex has been experimentally disrupted impairing the GR retrotransport, that is, by using the Hsp90 inhibitor geldanamycin, by overexpression of the TPR domain peptide that prevents the Hsp90•IMM interaction, or by overexpression of the PPIase domain peptide that prevents the IMM•dynein interaction. Also, the overexpression of p50/dynamitin (Dyt) subunit of dynactin interferes with the proper assembly of the dynein/dynactin motor complex. Both geldanamycin and overexpression of the TPR peptide interfere with the association of the oligomeric complex with structures of the nuclear pore making the nuclear accumulation of the receptor slower. (B) Nuclear translocation rate after the addition of steroid at zero time. The dotted red line represents the translocation rate measured when the transport machinery is disrupted in the points shown in panel A.