Trafficking of Nuclear Receptors in Living Cells

Most of the steroid receptor family, with the exception of the estrogen receptor, are classically viewed as 'translocating receptors'. That is, they move from an exclusively, or principally, cytoplasmic distribution in the absence of hormone to a predominately nuclear localization in hormone stimulated cells. The estrogen receptor and the nuclear receptor family are found exclusively in the nucleus, both in hormone stimulated and hormone free cells. This behavior has now been studied with GFP-fusions in living cells, and has in general been confirmed. However, there are important exceptions, and new findings, particularly with regard to sub-nuclear localization. We propose that the intracellular distribution of both receptor classes is dependent not only on subcellular localization signals directly encoded in the receptors, but also on the nature and composition of the large, macromolecular complexes formed by each receptor. Furthermore, we find that most members of the receptor superfamily form focal accumulations within the nucleus in response to ligand, and suggest that these structures may participate in the biological life cycle of the receptors. Finally, we propose that receptor movement in the nucleus is highly dynamic, with the receptors undergoing constant exchange between genomic regulatory elements, multi-protein complexes with other transcription factor partners, and subnuclear structures that are as yet poorly defined.