Premium
Molecular mechanisms involved in the constitutive nuclear localization of the mineralocorticoid receptor in cardiac myocytes
Author(s) -
Rosa Diego Alvarez,
HernandezDiaz Ivan,
Giraldez Teresa
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1040.11
Subject(s) - mineralocorticoid receptor , nuclear receptor , receptor , biology , medicine , endocrinology , microbiology and biotechnology , nuclear localization sequence , nuclear export signal , subcellular localization , myocyte , nucleus , aldosterone , cell nucleus , cytoplasm , transcription factor , gene , biochemistry
The mineralocorticoid receptor (MR) is a member of the nuclear receptor family. Aldosterone activates MR in target epithelia, modulating the expression of genes that enhance sodium reabsorption. In addition, MR may have other physiological functions. Altered expression/activation of cardiac MR leads to the development of cardiac fibrosis and MR blockade is beneficial for the treatment of heart failure. However, the physiological role and activation status of MR in the heart are poorly known. Since steroid receptors are typically cytoplasmic and translocate to the nucleus upon ligand binding, we examined the subcellular localization of MR. Our results show that MR is a constitutive chromatin‐bound factor in mouse left ventricle and in HL‐1 cardiomyocytes, regardless of corticosteroid levels. MR constitutive nuclear localization depends on two nuclear localization signals (NLS0 and NLS1), which are also essential for MR activity. Overexpression of hsp90 prevents the constitutive nuclear localization of MR, suggesting that heat shock protein expression levels could be a limiting factor in mouse cardiac myocytes, shifting the equilibrium of MR localization to the nucleus. The nuclear localization of MR in cardiac myocytes may have important consequences for its function and pharmacological regulation. This work was supported by grant BFU2007‐61148 from Ministerio de Ciencia e Innovación (Spain) to DAR.