Chaperoning Nuclear Mobility

Abstract

Nuclear receptors for steroid hormones are highly mobile within the nucleus. These hormones are ligand-regulated transcription factors that function as components of large macromolecular complexes containing various coactivators and corepressors, However, the underlying mechanisms and specific proteins mediating mobility of nuclear proteins are poorly understood. Elbi et al. developed an in situ assay with which to visualize protein movement in transcriptionally active nuclei. They discovered that molecular chaperones acted as mobility factors for nuclear steroid receptors. The authors treated murine adenocarcinoma cell lines expressing fluorescently labeled glucocorticoid receptors (GRs) or progesterone receptors (PRs) with digitonin permeabilization and hypotonic buffer extraction. Thus, they obtained cells with transcriptionally active nuclei that were depleted of soluble factors required for steroid receptor mobility, as assessed by fluorescence recovery after photobleaching. Incubating permeabilized and extracted cells with reticulocyte lysate restored GR and PR nuclear mobility, as did incubation with mixtures of chaperones and cochaperones. Restoration of mobility by both lysate and the chaperone mixtures depended on the presence of adenosine triphosphate. Treatment with dexamethasone (a ligand for GR) or R5020 (a ligand for PR) slowed the recovery of mobility of their respective receptors in response to treatment with lysate or chaperones. Molecular chaperones--which had previously been implicated in the assembly of steroid receptor complexes--thus appear to function as nuclear mobility factors involved in the regulation of GR and PR activity. C. Elbi, D. A. Walker, G. Romero, W. P. Sullivan, D. O. Toft, G. L. Hager, D. B. DeFranco, Molecular chaperones function as steroid receptor nuclear mobility factors. Proc. Natl. Acad. Sci. U.S.A. 101 , 2876-2881 (2004). [Abstract] [Full Text]