Biochemical insights into the evolution of alpha-catenin function in metazoan epithelia
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 |
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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 | |
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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 |
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Bibliographic information
Statement of responsibility | Phillip Wayne Miller. |
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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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