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Vitamin D receptor and retinoid X receptor interactions in motion
1Laboratory of Cell Biochemistry and Biology, National Institutes of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA. jul@helix.nih.gov
Abstract:
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.
Insights
Retinoid X receptor (RXR) dimerization is crucial for Vitamin D receptor (VDR) function, influencing gene transcription. New research reveals dynamic VDR-RXR interactions within cells, impacting VDR
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Vitamin D receptor (VDR) and retinoid X receptor (RXR) are nuclear receptors that form heterodimers to regulate gene transcription.
- Dimerization with RXR is essential for VDR's ligand-dependent and ligand-independent functions.
Purpose of the Study:
- To review the latest findings on RXR's role in VDR function.
- To explore the dynamic nature of VDR-RXR heterodimerization and its implications.
Main Methods:
- Literature review of biochemical, structural, and genetic studies.
- Analysis of recent microscopy studies using fluorescent protein chimeras in living cells.
Main Results:
- RXR dimerization is vital for VDR's roles in calcium homeostasis, bone development, cell growth, and hair growth.
- VDR and RXR exhibit dynamic shuttling between cellular compartments.
- Receptor-DNA and receptor-coregulator interactions are transient.
Conclusions:
- RXR's role in regulating VDR dynamics has broad significance due to RXR's promiscuous dimerization.
- Understanding these dynamic interactions offers new perspectives on nuclear receptor function.