Apico-basal distribution of the GPCR Smoothened and its impact on Hedgehog transduction

During development, the fate of epithelial cells is controlled by signalling molecules. Epithelial cells display an apico-basal polarity that results in an asymmetric distribution of proteins and lipids. The aim of my project is to understand how apico-basal polarity can modulate cell signalling in the context of the seven-pass transmembrane protein Smoothened (SMO), an oncogene which is required for the transduction of the Hedgehog (HH) morphogenetic signal.

Thanks to a novel method, I could label and follow the SMO molecules present at the surface of epithelial cells from the fly wing primordium, a structure whose development is under HH control.

I could thereby observe a basal enrichment of SMO at the surface of the cells that receive the highest levels of HH. My data support a model in which SMO is initially targeted to the apical region of epithelial cells, before being endocytosed and redistributed to the basal region, where it is stabilized in presence of HH. Finally, I showed that this basal accumulation of SMO requires its phosphorylation by a Protein Kinase A (PKA), Casein Kinase I (CKI) and the kinase called Fused (Fu), a known positive regulator of HH signalling.