Hedgehog Signaling Research Paper

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INTRODUCTION Hedgehog signaling has been implicated as playing crucial roles in the control of cell growth and patterning during embryonic development and other physiological processes in both Drosophila and vertebrates. Given these important physiological roles, it was of no surprise that disruption of Hh signaling was found to be the underlying cause of numerous human developmental disorders and that perturbations of Hh signaling play a causative or facilitating role in many human cancers (5–7 Cell Network). Motivated by the important role Hh has in cancer, researchers are trying to unlock the still largely unknown mechanistic understanding of Hh signal transduction. Hh signaling is transduced through a series of molecular interactions …show more content…

showed that phosphorlyation is not neccessary for Smo translocation but rather inhibition of Smo endocytosis was sufficient to drive Smo to the plasma membrane. This was observed by fluorescently labelling Smo with GFP and tracking its location following either treatment with Hh or Dynasore, a pharmacological inhibitor of dynamin-mediated endocytosis (Macia et al., 2006). In both cases Smo translocated to the plasma membrane. The same was done for a nonphosphorylatable SmoSA-GFP fusion in which the inhibition of endocytosis by treatment with Dynasore caused SmoSA to translocation to the plasma membrane. The observation that SmoSA can also be present at the membrane demonstrates that some exchange between the intracellular and plasma membrane bound pools must also occur for nonphosphorylated …show more content…

Additionally, inactivation of Ptc is sufficient to increase levels of this phospholipid (Yavari et al., 2010). These observations support an ‘endocytosis’ model of Hh pathway activation, whereby inactivation of Ptc primarily affects Smo redistribution to the plasma membrane, presumably by regulating the local lipid content of either the plasma membrane or Smo containing endosomes. This suggests Ptc inactivation by Hh first drives Smo membrane localisation by modulating membrane phospholipids, with Smo phosphorylation and clustering occurring

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