Ligand-dependent contribution of RXRbeta to cholesterol homeostasis in Sertoli cells.
Journal:
EMBO Rep. 2004 MarAuthors:
Mascrez B, Ghyselinck NB, Watanabe M, Annicotte JS, Chambon P, Auwerx J, Mark M
Abstract
We show that mice expressing retinoid X receptor beta (RXRbeta) impaired in its transcriptional activation function AF-2 (Rxrb(af20) mutation) do not display the spermatid release defects observed in RXRbeta-null mutants, indicating that the role of RXRbeta in spermatid release is ligand-independent. In contrast, like RXRbeta-null mutants, Rxrb(af20) mice accumulate cholesteryl esters in Sertoli cells (SCs) due to reduced ABCA1 transporter-mediated cholesterol efflux. We provide genetic and mole
...[more]cular evidence that cholesterol homeostasis in SCs does not require PPARalpha and beta, but depends upon the TIF2 coactivator and RXRbeta/LXRbeta heterodimers, in which RXRbeta AF-2 is transcriptionally active. Our results also indicate that RXRbeta may be activated by a ligand distinct from 9-cis retinoic acid.[less]
Mesh Headings:
ATP-Binding Cassette Transporters, Animals, Cholesterol, DNA-Binding Proteins, Dimerization, Electrophoretic Mobility Shift Assay, Gene Expression Regulation, Gene Silencing, Histone Acetyltransferases, Homeostasis, Immunochemistry, Ligands, Male, Mice, Mice, Knockout, Nuclear Receptor Coactivator 1, Nuclear Receptor Coactivator 2, Orphan Nuclear Receptors, Protein Binding, Receptors, Cytoplasmic and Nuclear, Retinoid X Receptor beta, Sertoli Cells, Spermatids, Transcription Factors