ArticleCellular and molecular life sciences : CMLS2022
PI(4,5)P2 controls slit diaphragm formation and endocytosis in Drosophila nephrocytes.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Endosomal maturation is controlled by the trimeric Bulli-Mon1-Ccz1 Rab7 GEF complex and the Rab5 GTPase-activating protein GAPsec.Journal of cell science · 2026Article
- The lipid-podocyte axis: emerging clues in membranous nephropathy pathogenesis.Frontiers in medicine · 2026Review
- Combined transcriptome and proteome profiling reveal cell-type-specific functions of Drosophila garland and pericardial nephrocytes.Communications biology · 2024Article
- Phospholipid scramblase 1: an essential component of the nephrocyte slit diaphragm.Cellular and molecular life sciences : CMLS · 2024Article
- Insights into human kidney function from the study of Drosophila.Pediatric nephrology (Berlin, Germany) · 2023Review
- An acytokinetic cell division creates PIP2-enriched membrane asymmetries leading to slit diaphragm assembly in Drosophila nephrocytes.Development (Cambridge, England) · 2023Article
- Network pharmacology and molecular docking of endogenous active metabolites in diabetic kidney disease.Renal failure · 2023Article
- Endocytosis at the Crossroad of Polarity and Signaling Regulation: Learning fromInternational journal of molecular sciences · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
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Abstract
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 to strongly reduced endocytosis. Notably, reduction in PI(3,4,5)P3 by overexpression of PTEN or expression of a dominant-negative phosphatidylinositol-3-kinase did not affect nephrocyte function, whereas enhanced formation of PI(3,4,5)P3 by constitutively active phosphatidylinositol-3-kinase resulted in strong slit diaphragm and endocytosis defects by ectopic activation of the Akt/mTOR pathway. Thus, PI(4,5)P2 but not PI(3,4,5)P3 is essential for slit diaphragm formation and nephrocyte function. However, PI(3,4,5)P3 has to be tightly controlled to ensure nephrocyte development.
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