Vitamin D receptor and retinoid X receptor interactions in motion.
Vitamin D receptor (VDR) and retinoid X receptor (RXR) are members of the nuclear receptor superfamily and they bind target DNA sequences as heterodimers to regulate transcription. This article surveys the latest findings regarding the roles of dimerizing RXR in VDR function and emphasizes potential areas for future developments. We first highlight the importance of dimerization with RXR for both the ligand-independent (hair growth) and ligand-dependent functions of VDR (calcium homeostasis, bone development and mineralization, control of cell growth and differentiation). Emerging information regarding the regulatory control of dimerization based on biochemical, structural, and genetic studies is then presented. Finally, the main focus of this article is a new dynamic perspective of dimerization functions, based on recent research with fluorescent protein chimeras in living cells by microscopy. These studies revealed that both VDR and RXR constantly shuttle between the cytoplasm and the nucleus and between subnuclear compartments, and showed the transient nature of receptor--DNA and receptor--coregulator interactions. Because RXR dimerizes with most of the nuclear receptors, regulation of receptor dynamics by RXR has a broad significance.
Barsony
J
J
Laboratory of Cell Biochemistry and Biology, National Institutes of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA. jul@helix.nih.gov
Prufer
K
K
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000502:physiology*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic
D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D004247:DNA; D002117:Calcitriol; D002118:Calcium