biostudies-literatureGass MMWestfälische Wilhelms-Universität Münsterdeutsche forschungsgemeinschaft248https://www.ebi.ac.uk/biostudies/studies/S-EPMC9016003biostudies-literatureUnknown79(5)Drosophila nephrocytes are an emerging model system for mammalian podocytes and proximal tubules as well as for the investigation of kidney diseases. Like podocytes, nephrocytes exhibit characteristics of epithelial cells, but the role of phospholipids in polarization of these cells is yet unclear. In epithelia, phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) and phosphatidylinositol(3,4,5)-trisphosphate (PI(3,4,5)P3) are asymmetrically distributed in the plasma membrane and determine apical-basal polarity. Here, we demonstrate that both phospholipids are present in the plasma membrane of nephrocytes, but only PI(4,5)P2 accumulates at slit diaphragms. Knockdown of Skittles, a phosphatidylinositol(4)phosphate 5-kinase, which produces PI(4,5)P2, abolished slit diaphragm formation and led tCellular and molecular life sciences : CMLSPI(4,5)P2 controls slit diaphragm formation and endocytosis in Drosophila nephrocytes.PMC9016003SFB1348-A03SFB1348-A05Krahn MPNedvetsky PBorkowsky SMissler MSiwek RLotz MLLuschnig SSchroter RRohlmann AGass MMfalsePI(4,5)P2 controls slit diaphragm formation and endocytosis in Drosophila nephrocytes.Drosophila nephrocytes are an emerging model system for mammalian podocytes and proximal tubules as well as for the investigation of kidney diseases. Like podocytes, nephrocytes exhibit characteristics of epithelial cells, but the role of phospholipids in polarization of these cells is yet unclear. In epithelia, phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) and phosphatidylinositol(3,4,5)-trisphosphate (PI(3,4,5)P3) are asymmetrically distributed in the plasma membrane and determine apical-basal polarity. Here, we demonstrate that both phospholipids are present in the plasma membrane of nephrocytes, but only PI(4,5)P2 accumulates at slit diaphragms. Knockdown of Skittles, a phosphatidylinositol(4)phosphate 5-kinase, which produces PI(4,5)P2, abolished slit diaphragm formation and led t2022-01-01T00:00:00Z2022 Apr2025-04-22T19:06:49.818Z2025-02-19T01:23:47.931ZS-EPMC90160033543769610.1007/s00018-022-04273-7