Phosphatidylinositol 4,5-bisphosphate directly interacts with the β and γ subunits of the sodium channel ENaC.

ABSTRACT: The plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP₂) regulates the activity of diverse ion channels to include the epithelial Na⁺ channel ENaC. Whether PIP₂ regulation of ENaC is due to a direct phospholipid-protein interaction, remains obscure. To date, possible interaction of PIP₂ with ENaC primarily has been tested indirectly through assays of channel function. A fragment-based biochemical analysis approach is used here to directly quantify possible PIP₂-ENaC interactions. We find using the CIBN-CRY2 optogenetic dimerization system that the phosphoryl group positioned at carbon 5 of PIP₂ is necessary for interaction with ENaC. Previous studies have implicated conserved basic residues in the cytoso

SUBMITTER: Archer CR 

PROVIDER: S-EPMC7278353 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature