Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P41181 (
collecting duct
)
5,183
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The molecular mechanisms of aldosterone-regulated Na+ transport are not entirely clear. The goal of this study was to identify aldosterone-induced genes potentially involved in the trafficking of the epithelial Na+ channel (ENaC). We report that the transcript levels of
melanophilin
(
MLPH
), a protein involved in vesicular trafficking in melanocytes, are rapidly increased by aldosterone in cortical
collecting duct
(
CCD
) cells. This effect was near maximal at physiological aldosterone concentrations, indicating that it is mediated by the mineralocorticoid receptor. De novo protein synthesis is not required for the induction of
MLPH
mRNA by aldosterone. To determine whether this induction has functional consequences on transepithelial Na+ current, we generated clonal
CCD
cell lines that express a tetracycline-inducible
MLPH
. Induction of
MLPH
in these cells led to a relatively modest, but statistically significant, increase in amiloride-sensitive Na+ current, suggesting the
MLPH
may be involved in ENaC trafficking. MyosinVc, the epithelial-specific class V myosin that is highly homologous to MyosinVa, another component of the melanosome trafficking complex, has putative consensus sites for serum and glucocorticoid-induced kinase 1 (SGK1), an early aldosterone-induced kinase that mediates some of aldosterone's effects on Na+ transport. Our results indicate that MyosinVc is phosphorylated by endogenous SGK1, suggesting that this complex may be involved in the aldosterone-regulated trafficking of ENaC in the
CCD
. These results suggest potential mechanisms by which aldosterone may regulate Na+ transport both directly, by increasing the abundance of
MLPH
, and indirectly by increasing the transcription of SGK1, which in turn regulates the activity of MyosinVc.
...
PMID:Melanophilin, a novel aldosterone-induced gene in mouse cortical collecting duct cells. 1760 87
