INVESTIGATING THE FUNCTION OF shc-3 IN THE INSULIN/INSULIN-LIKE SIGNALING PATHWAY IN CAENORHABDITIS ELEGANS

Abstract

The insulin/insulin-like signaling pathway (IIS) is an evolutionarily conserved metabolic pathway. The model organism, Caenorhabditis elegans, can provide insight into the structure and regulation of the pathway. Shc proteins are scaffold proteins that assist in phosphorylation-dependent complex formation. The Shc protein SHC-3 was recently identified in the MacNeil lab. Genetically, SHC-3 functions in the IIS pathway to regulate stress response and survival during L1 arrest; however, its exact role in this pathway is unknown. SHC-3 is localized to the cytosol at low temperatures and at the apical membrane at high temperatures. This project aimed to identify regulators of SHC-3 localization through a combination of forward and reverse genetics approaches. RNAi knockdown and an unbiased mutagenesis screen were used to identify regulators of SHC-3. The work from this project suggests that SHC-3 is regulated by a Transforming Growth Factor-β (TGF-β) pathway. Candidate SHC-3 interacting proteins were also identified using a proximity labeling protocol.