Nurr1-RXR heterodimers mediate RXR ligand-induced signaling in neuronal cells
The retinoid X receptor (RXR) is essential as a common heterodimerization partner of several nuclear receptors (NRs). However, its function as a bona fide receptor for endogenous ligands has remained poorly understood. Such a role would depend on the existence of RXR activating ligands in vivo and o...
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Published in | Genes & development Vol. 17; no. 24; pp. 3036 - 3047 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Cold Spring Harbor Laboratory Press
15.12.2003
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Subjects | |
Online Access | Get full text |
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Summary: | The retinoid X receptor (RXR) is essential as a common heterodimerization partner of several nuclear receptors (NRs). However, its function as a bona fide receptor for endogenous ligands has remained poorly understood. Such a role would depend on the existence of RXR activating ligands in vivo and on the ability of such ligands to influence relevant biological functions. Here we demonstrate the presence of endogenous RXR ligands in the embryonic central nervous system (CNS) and show that they can activate heterodimers formed between RXR and the orphan NR Nurr1 in vivo. Moreover, RXR ligands increase the number of surviving dopaminergic cells and other neurons in a process mediated by Nurr1-RXR heterodimers. These results provide evidence for a role of Nurr1 as a ligand-independent partner of RXR in its function as a bona fide ligand-activated NR. Finally, our findings identify RXR-Nurr1 heterodimers as a potential target in the treatment of neurodegenerative disease. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 These authors contributed equally to this work. Corresponding author. E-MAIL Thomas.Perlmann@licr.ki.se ; FAX 46-8-33-28-12. Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.276003. |
ISSN: | 0890-9369 1549-5477 |
DOI: | 10.1101/gad.276003 |