Biochemical insights into the evolution of alpha-catenin function in metazoan epithelia
- Alpha-catenin is a multi-functional adhesion protein that links cadherin and beta-catenin at the adherens junction to the underlying cortical actin cytoskeleton, and regulates actin dynamics in the cytoplasm. Alpha-catenin is essential for the formation of stable cell-cell contacts, and depletion results in gross developmental defects and cancer. While all animals have homologs of alpha-catenin, previous work from the Nelson and Weis labs demonstrated surprising functional differences between alpha-catenin homologs from M. musculus, C.elegans, and D. discoideum. These studies lacked sufficient phylogenetic coverage to make broad interpretations about the evolution of the cadherin-catenin complex and epithelial tissues. To address this gap in the literature, I reviewed previous data about the evolution of alpha-catenin and performed sequence analysis on animals and their near ancestors to make hypotheses about how the cadherin-catenin complex may have evolved (Chapter 1). I then investigated the biochemical properties of alpha-catenin homologs from three phylogenetic groups crucial to our understanding of the evolution of the cadherin-catenin complex but not before studied. Namely, an α-catenin homolog from a close outgroup to mammals (the zebrafish Danio rerio; Chapter 2), the closest outgroup to bilaterians (the sea anemone Nematostella vectensis; Chapter 3), and one of the earliest branching animal lineages (the marine sponge Oscarella carmela; Chapter 4) were characterized biochemically. This study reinforces the importance of biochemical characterization in studies of protein evolution as all three homologs possess distinct biochemical profiles from previously annotated alpha-catenins. Most importantly, this study provides a framework for future discussion about the evolution of the cadherin-catenin complex in animals and its role in the development of organized epithelial tissues (Chapter 5).
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|2015 - 2016; 2015, c2016
|Miller, Phillip Wayne
|Stanford University, Department of Molecular and Cellular Physiology.
|Weis, William I
|Weis, William I
|Statement of responsibility
|Phillip Wayne Miller.
|Submitted to the Department of Molecular and Cellular Physiology.
|Thesis (Ph.D.)--Stanford University, 2016.
- © 2016 by Phillip Wayne Miller
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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