Biochemical insights into the evolution of alpha-catenin function in metazoan epithelia

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Abstract/Contents

Abstract
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).

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2015 - 2016; 2015, c2016
Issuance monographic
Language English

Creators/Contributors

Associated with Miller, Phillip Wayne
Associated with Stanford University, Department of Molecular and Cellular Physiology.
Primary advisor Nelson, William
Thesis advisor Nelson, William
Thesis advisor Nachury, Maxence
Thesis advisor O'Brien, Lucy
Thesis advisor Weis, William I
Advisor Nachury, Maxence
Advisor O'Brien, Lucy
Advisor Weis, William I

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Phillip Wayne Miller.
Note Submitted to the Department of Molecular and Cellular Physiology.
Thesis Thesis (Ph.D.)--Stanford University, 2016.
Location electronic resource

Access conditions

Copyright
© 2016 by Phillip Wayne Miller
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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