Synaptojanin regulates Hedgehog signalling by modulating phosphatidylinositol 4-phosphate levels
In Hedgehog (Hh) signalling, Hh ligand concentration gradient is effectively translated into a spatially distinct transcriptionalprogram to give precisely controlled context dependent developmental outcomes. In the absence of Hh, the receptorPatched (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 wingdiscsof Drosophila melanogaster, this study shows that Synaptojanin (Synj), a dual phosphatase, modulates PI(4)P levelsand affects Smo activation, and thereby functions as an additional regulatory step in the Hh pathway. Reducing the levels ofSynj in the wing-discs caused enhancement of a Hh dominant gain-of-function Moonrat phenotype in the adult wings. Synjdownregulation augmented Hh signalling, which was associated with elevated PI(4)P levels and Smo activation. Synj didnot control the absolute pathway activity but rather fine-tuned the response since its downregulation increased expression ofdecapentaplegic (dpp), a low-threshold target of the pathway while the high-threshold targets remained unaffected. This isthe first report that identifies Synj as a negative regulator of Hh signalling, implying its importance and an additionalregulatory step in Hh signal transduction.
Volume 44 | Issue 6
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