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Melanophilin and myosinVc: potential players in ENaC trafficking are regulated by aldosterone
Author(s) -
Martel Jessica Armstrrong,
FejesToth Geza,
NarayFejesToth Aniko
Publication year - 2007
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.21.6.lb110-d
Subject(s) - aldosterone , epithelial sodium channel , mineralocorticoid receptor , mineralocorticoid , biology , microbiology and biotechnology , endocrinology , medicine , chemistry , sodium , organic chemistry
The molecular mechanisms of aldosterone‐regulated Na + transport are not entirely clear. The goal of this study was to identify aldosterone‐induced genes that could be involved in trafficking of the epithelial Na + channel (ENaC). We report that transcript levels of melanophilin (MLPH), a protein involved in vesicular trafficking, are rapidly and directly increased by aldosterone in mouse cortical collecting duct (CCD) cells. This effect was near maximal at physiological aldosterone concentrations indicating that it is mediated by the mineralocorticoid receptor and likely has biological significance. To determine if this induction is functionally relevant, we generated clonal CCD cell lines that over‐express a tet‐inducible mMLPH. Over‐expression of MLPH led to a significant increase in Na + current, suggesting the MLPH may be involved in ENaC trafficking. Our findings also suggest that MyosinVc is phosphorylated by endogenous serum and glucocorticoid‐induced kinase 1, an early aldosterone‐induced gene that mediates the effects of aldosterone in Na + transport. MyosinVa is an essential member of the melanosome trafficking complex. MyosinVc is the epithelial‐specific class V myosin and may therefore be involved in ENaC trafficking in the CCD. These results suggest alternative mechanisms by which aldosterone may be regulating Na + transport. Research supported by NIH grants DK41841, DK55845 and DK58898.