ATP8B1 regulates PIP2 localization and cleavage of pyroptotic executioner Gasdermin D.

ABSTRACT: Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis, with symptoms including pruritus, pancreatitis, fat malabsorption, intestinal inflammation, and failure to thrive. High-throughput studies showed interconnection between ATP8B1 and phosphoinositide (PIPs), but the mechanism linking ATP8B1, lipid metabolism, and inflammation remains unclear. Atp8b1^G308V/G308V mouse model, unbiased RNAseq, high-resolution-stimulation emission depltion (STED)-microscopy, and Crispr-Cas9 generated ATP8B1^-/- knockouts in hepatocytes/monocytes/macrophages were used to determine role of ATP8B1 in phosphatidylinositol,4-5-bisphosphate (PIP2) trafficking and inflammation. Human ATP8B1, purified from Sf9 insect cells and reconstituted in proteoliposome

SUBMITTER: Bhandari N 

PROVIDER: S-EPMC12146700 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature