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Hedgehog is a morphogen that is carried on lipoproteins and that regulates patterning and proliferation. Hyperactivity of Hedgehog signaling causes numerous forms of cancer. Hedgehog acts via relieving repression of Smoothened by Patched - the mechanism of this repression has been unclear. The structural homology of Patched with bacterial transmembrane transporters suggests that Patched might regulate lipid trafficking to repress Smoothened. However, no endogenous lipid regulators of Smoothened have yet been identified, nor has it ever been shown that Patched actually controls lipid trafficking. This work shows that, in Drosophila melanogaster, Patched regulates Smoothened trafficking from Patched-positive endosomes. Furthermore, it demonstrates that Patched recruits internalized lipoproteins to these endosomes, thereby regulating the efflux of specific lipoprotein-derived lipids from this compartment and utilizing these lipids to repress Smoothened. We propose that Patched normally promotes Smoothened degradation and inhibits its activity by utilizing a specific lipoprotein-derived lipid. Further, we suggest that presence of Hedgehog on lipoproteins prevents their utilization.

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Helena Khaliullina-Skultety wurde 1982 in Kazan, Russland geboren und kam mit 17 Jahren nach Deutschland. Sie studierte Technische Biologie an der Universität Stuttgart und Nanyang University Singapur. Nach dem erfolgreichen Studium promovierte sie 2010 am Max-Planck-Institut für molekulare Zellbiologie und Genetik in Dresden mit magna cum laude.

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