Trafficking of nuclear receptors in living cells

Most of the steroid receptor family, with the exception of the estrogen rec eptor. are classically viewed as 'translocating receptors'. That is, they m ove from an exclusively, or principally, cytoplasmic distribution in the ab sence of hormone to a predominately nuclear localization in hormone stimula ted cells. The estrogen receptor and the nuclear receptor family are found exclusively in the nucleus, both in hormone stimulated and hormone free cel ls. This behavior has now been studied with GFP-fusions in living cells, an d has in general been confirmed. However, there are important exceptions, a nd new findings, particularly with regard to sub-nuclear localization. We p ropose that the intracellular distribution of both receptor classes is depe ndent not only on subcellular localization signals directly encoded in the receptors, but also on the nature and composition of the large, macromolecu lar complexes formed by each receptor. Furthermore, we find that most membe rs 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 recep tor movement in the nucleus is highly dynamic, with the receptors undergoin g constant exchange between genomic regulatory elements, multi-protein comp lexes with other transcription factor partners, and subnuclear structures t hat are as yet poorly defined. Published by Elsevier Science Ltd.