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Characterizing aPKC signaling substrates and binding partners in cell polarity

Grant number: 15/24046-5
Support type:Scholarships abroad - Research
Effective date (Start): May 20, 2016
Effective date (End): May 19, 2017
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Deborah Schechtman
Grantee:Deborah Schechtman
Host: Sourav Ghosh
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Yale School of Medicine (YSM), United States  

Abstract

Cell polarity is essential for differentiation, growth of budding yeast, asymmetric cell division, morphogenesis, transport of molecules across epithelial layers, cell migration and transmission of nerve impulse (enabled by axonal specification and morphological polarity of neurons) amongst other processes. Atypical protein kinase c (aPKC) has been described as a key component in determining cell polarity by interacting with the Partitioning defective complex (Par complex). In fact aPKCs have a role in maintaining cell polarity in several cells including the fertilized egg and epithelial cells. Specifically with regards to neuronal polarization, previous studies from the Ghosh lab have shown that aPKCiota plays an important role in specifying the axon. In contrast, the differentially regulated form of PKCzeta named PKMzeta which lacks the regulatory domain of PKCzeta, has a key role in inhibiting neurites from becoming axons. Both proteins can bind Par3 and their antagonistic function is based on competition for Par3-binding. Loss of polarity is also a characteristic feature of cancer cells and epithelial mesenchymal transition (EMT). Recent unpublished studies from the Ghosh lab have observed PKMz expression in carcinomas. However, mechanisms of aPKC signaling, especially PKMz signaling, in these processes remain to be fully determined. Thus, in the present project we intend to identify and characterize aPKC substrates and binding proteins, including that of PKMz, and determine the signaling pathways that are involved in axon specification and epithelial polarity. The components and principles identified in this study can be extrapolated broadly to the regulation of cell polarity in general.