GIPC, a PDZ Protein Involved in NGF/TrkA Signalng and Trafficking

GIPC was originally identified in our lab based on its ability to bind to the RGS protein GAIP. GIPC is a PDZ protein that is located on endocytic vesicles and has been shown to interact with several growth factor receptors including the TrkA growth factor and the IGF-1 and TGF-βIII receptors. It also interacts with several other receptors, signaling molecules and motor proteins. This has led us to propose that GIPC, like some other PDZ proteins serves to organize signaling complexes and molecules regulating endocytosis.

To understand the functions of GIPC we are attempting to define GIPC’s interacting partners and trafficking using PC-12 cells stably expressing the TrkA receptor. In collaboration with the laboratory of John Yates we are using a proteomics approach to identify GIPC binding proteins and immunofluorescence and immunoelectron microscopy to determine their localization and trafficking, and Map kinase and neurite outgrowth assays to assess the effects of overexpression or knock-down (siRNA) of specific partners on TrkA trafficking.

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