Hedgehog-Regulated Ubiquitination Controls Smoothened Trafficking and Cell Surface Expression in Drosophila

• DOI: 10.1371/journal.pbio.1001239
• Publication Date: 2012-01-10T21:59:31Z
• Authors: Shuang Li; Yongbin Chen; Qing Shi; Tao Yue; Bing Wang; Jin Jiang
• Keywords: Smoothened; Deubiquitinating enzyme

Hedgehog transduces signal by promoting cell surface expression of the seven-transmembrane protein Smoothened (Smo) in Drosophila, but underlying mechanism remains unknown. Here we demonstrate that Smo is downregulated ubiquitin-mediated endocytosis and degradation, Hh increases inhibiting its ubiquitination. We find ubiquitinated at multiple Lysine residues including those autoinhibitory domain (SAID), leading to degradation both lysosome- proteasome-dependent mechanisms. inhibits ubiquitination via PKA/CK1-mediated phosphorylation SAID, accumulation. Inactivation ubiquitin activating enzyme Uba1 or perturbation components endocytic machinery leads accumulation pathway activation. In addition, non-visual β-arrestin Kurtz (Krz) interacts with acts parallel downregulate Smo. Finally, show counteracted deubiquitinating UBPY/USP8. Gain loss UBPY lead reciprocal changes expression. Taken together, our results suggest plays a key role downregulation keep activity off absence ligand, Hh-induced promotes ubiquitination, which contributes