Date of Award
Summer 8-22-2026
Document Type
Dissertation
Degree Name
Ph.D. in Biological Sciences
Organizational Unit
College of Natural Science and Mathematics, Biological Sciences
First Advisor
Erich J. Kushner
Second Advisor
Todd Blankenship
Third Advisor
Cedric Asensio
Fourth Advisor
Xi Yang
Copyright Statement / License for Reuse
All Rights Reserved.
Keywords
Cav1, Caveolae, EHD2, Endothelial Cells
Abstract
Caveolae are 50-100nm cholesterol rich flask shaped invaginations found in many differentiated cells. Namely, these structures have been seen to be abundant in endothelial cells where they are involved in many signaling contexts. However, under mechanical stress, the characteristics of caveolae alter, flattening to increase membrane compliance, while displaced proteins can shift from structural roles to mechanosensitive signaling functions. Caveolin-1 (Cav1) is the principal protein required for Caveolar formation while Eps15 Homology Domain Containing Protein 2 (EHD2) is a membrane ATPase that acts to stabilize caveolae at the surface. Despite their emerging importance, understanding the organization and dynamic regulation of this structure remains challenging in cell biology.
This research investigates the spatiotemporal organization of caveolae and EHD2’s role in caveolar organization and motility. Using endothelial cells, I examined how caveolae are organized in polar environments to gain an understanding of how perturbations in this axis are influenced by the presence of the regulatory protein EHD2.
I found that reduction of EHD2 impairs the stabilization and function of caveolae producing defects in focal adhesion (FA) composition and turnover. Particularly, loss of EHD2 reduced maintenance of key focal adhesion-associated components, extending the associating of zyxin to mature focal adhesions. These defects were accompanied by changes in β1- integrin trafficking, supporting a role for caveolae in coordinating integrin availability at the plasma membrane with adhesion maturation.
Comparative analysis of both EHD2 and Caveolin-1 deficient cells further revealed distinct roles for these proteins. While both perturbations impaired endothelial adhesion organization, the data supports a model in which Cav1 is required for the overall caveolar structure while EHD2 regulates the accessibility and stabilization in a way that is important for membrane tension adaptation and focal adhesion turnover.
Together, this work establishes EHD2 as a critical regulator of caveolae dependent integrin trafficking and focal adhesion dynamics as a central mechanism that links membrane mechanics to endothelial cell behavior. Leaning to the understanding that endothelial cells adapt to mechanical stress by suggesting that dysfunction of the Caveolae-EHD2 interaction may contribute to vascular instability and disease.
Copyright Date
8-2026
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Jasper Stanae Farrington
Provenance
Received from ProQuest
File Format
application/pdf
Language
English (eng)
Extent
131 pgs
File Size
3.7 MB
Recommended Citation
Farrington, Jasper Stanae, "Investigating Caveolar Systems: Spatiotemporal Quantification of Caveolin-1 and the Mechanotransducive Function of EHD2" (2026). Electronic Theses and Dissertations. 2766.
https://digitalcommons.du.edu/etd/2766