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Complex regulation of the epithelial Na+ channel (ENaC) by phosphatidylinsoitol bisphosphate (PIP 2 ).
Author(s) -
Edinger Robert S,
Kester Lauren,
Weixel Kelly M,
Johnson John P
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.21.5.a543-a
Subject(s) - epithelial sodium channel , microbiology and biotechnology , xenopus , chemistry , gene isoform , endocytic cycle , endocytosis , exocytosis , biology , biochemistry , receptor , sodium , gene , secretion , organic chemistry
Phosphatidylinositol‐5 kinase α (PIP5Kα) has been shown to stimulate PIP 2 production and induce exocytosis of ENaC, increasing surface expression. PIP 2 has also been shown to bind to ENaC and increase open probability. We present data that PIP5Kβ decreases ENaC activity and surface expression in both Xenopus oocytes and cultured collecting duct cells. This effect is dependent on increased levels of PIP 2 and involves an interaction with the adaptor protein epsin which promotes ENaC endocytosis. PIP4K3α, which produces the PIP 2 precursor PIP4, also down regulates ENaC activity in a kinase dependent manner, while the 2β isoform of PIP4K, which has been localized to the ER and endocytic structures, has no effect on ENaC activity. Expression of a membrane localized synaptojanin, a PIP2 phosphatase, down‐regulates ENaC activity suggesting it may reverse one of the stimulatory actions of PIP2; but does not reverse or affect the down‐regulation of ENaC induced by PIP5Kβ The data indicate that PIP2 generated by alternate isoforms of PIP5K or PIP4K have dramatically differing effects on ENaC expression and activity. Distinct spatial localization of kinases results in differing effects on channel function.