Regulatory mechanisms of wingless degradation

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Project objective

Wingless is a secreted glycoprotein that acts as a morphogen and plays fundamental roles in body patterning and cell differentiation. To prevent ectopic signaling, mechanisms have evolved that confine its range of action. One such mechanism has been discovered by the group that I am joining. In Drosophila embryos, the action of Wingless towards the posterior is limited by an EGFR -regulated pathway that targets this molecule for lysosomal degradation. My aim is to uncover the cell biological basis of this phenomenon. Using a genetic approach, I will identify the receptor(s) of Wingless that are responsible for its degradation. I will then study biochemically whether the receptor(s) undergo( es) post-translational modifications that might regulate the degradation process. The receptors will also be mutagenised in vitro and their ability to mediate degradation assayed. Together, these two approaches will allow me to map the sites, within the cytoplasmic tail of those receptors, that are required for regulated lysosomal targeting. In parallel I will identify additional proteins that regulate the degradation process. This will be done in two different ways:1 ) using RNA-i to test the role of candidate molecules and2) isolating biochemically proteins that interact with the receptor only at the stage when the degradation process is activated.

Original text from CORDIS.

Participants

• MRC National Institute for Medical Research · LondonCoordinatorUnited Kingdom

Links

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