P2Y receptor trafficking in polarized epithelial cells

DuBose, Darrell R.

P2Y receptor trafficking in polarized epithelial cells Public Deposited

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March 22, 2019

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DuBose, Darrell R.
- Affiliation: School of Medicine, Department of Pharmacology

Abstract

A layer of interconnected epithelial cells line the organs of the human body. These cells have three functions: absorption of nutrients, secretion of wastes, and protection from pathogens. Chemically, epithelial cells are the mediators of nearly all interactions between the body and the world around us. In order to function properly, epithelial cells must maintain two distinct membrane regions with unique protein and lipid compositions. Disruption of these compositions results in diseases like cystic fibrosis, retinitis pigmentosa, nephrogenic diabetes insipidus, Dubin-Johnson syndrome, and polycystic kidney disease. To this day, many of the mechanisms underlying apical versus basolateral protein sorting remain unknown. The work presented here is focused on the sorting of the P2Y family of G protein coupled receptors and the transport of receptors between the apical and basolateral membrane regions of epithelial cells. Two separate but linked projects are detailed in this thesis. The first project details the delimitation and determination of key amino acids in the apical targeting sequence of the P2Y?4? receptor. The second project describes the development of a novel technique for determining the trafficking itineraries of proteins in polarized epithelial cells that is then applied to understand the trafficking mechanisms for the P2Y?1?, P2Y?2?, and P2Y?4? receptors. Together, these studies highlight the complexity and diversity of sorting and trafficking mechanisms at work in epithelial cells and suggest methods by which they may be better understood.

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