1. Synaptojanin regulates Hedgehog signalling by modulating phosphatidylinositol 4-phosphate levels.
- Author
-
Ahaley SS
- Subjects
- Animals, Drosophila Proteins metabolism, Drosophila melanogaster metabolism, Gene Expression Regulation, Genes, Reporter, Genotype, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Hedgehog Proteins metabolism, Nerve Tissue Proteins metabolism, Phenotype, Phosphoric Monoester Hydrolases metabolism, Receptors, Cell Surface genetics, Receptors, Cell Surface metabolism, Signal Transduction, Smoothened Receptor metabolism, Transcription Factors genetics, Transcription Factors metabolism, Drosophila Proteins genetics, Drosophila melanogaster genetics, Hedgehog Proteins genetics, Nerve Tissue Proteins genetics, Phosphatidylinositol Phosphates metabolism, Phosphoric Monoester Hydrolases genetics, Smoothened Receptor genetics, Wings, Animal metabolism
- Abstract
In Hedgehog (Hh) signalling, Hh ligand concentration gradient is effectively translated into a spatially distinct transcriptional program to give precisely controlled context dependent developmental outcomes. In the absence of Hh, the receptor Patched (Ptc) inhibits the signal transducer Smoothened (Smo) by maintaining low phosphatidylinositol 4-phosphate (PI(4)P) levels. Binding of Hh to its receptor Ptc promotes PI(4)P production, which in turn activates Smo. Using wingdiscs of Drosophila melanogaster , this study shows that Synaptojanin (Synj), a dual phosphatase, modulates PI(4)P levels and affects Smo activation, and thereby functions as an additional regulatory step in the Hh pathway. Reducing the levels of Synj in the wing-discs caused enhancement of a Hh dominant gain-of-function Moonrat phenotype in the adult wings. Synj downregulation augmented Hh signalling, which was associated with elevated PI(4)P levels and Smo activation. Synj did not control the absolute pathway activity but rather fine-tuned the response since its downregulation increased expression of decapentaplegic (dpp) , a low-threshold target of the pathway while the high-threshold targets remained unaffected. This is the first report that identifies Synj as a negative regulator of Hh signalling, implying its importance and an additional regulatory step in Hh signal transduction.
- Published
- 2018