Understanding the functional link between adherens junctions and the cytoskeleton
Abstract/Contents
- Abstract
- This thesis focuses on understanding the functional link between the Adherens Junction (AJ) and the cytoskeleton. In order to control tissue integrity, the AJ complex links to the cytoskeleton, including actin and microtubules, and thereby controls intercellular adhesion, cell migration and the orientation of cell division. However, how AJ connection to the cytoskeleton is established and regulated is not well understood. Formation of the AJ is directed by the cadherin-catenin complex (CCC), which in epithelial cells comprises E-cadherin that binds β-catenin, which in turn recruits the F-actin binding and bundling protein αE-catenin. αE-Catenin is essential for cell-cell adhesion, and at cell-cell junctions is thought to link the CCC to F-actin either directly when under force, or indirectly by recruiting additional actin binding proteins (reviewed in Chapter 1). Mammalian αE-catenin also forms a homodimer in the cytosol, which is mutually exclusive with β-catenin binding in the CCC. However, even though the αE-catenin homodimer binds readily to F-actin and has been shown to inhibit Arp2/3 and cofilin activities, its role in cell-cell adhesion remains poorly understood. In Chapter 2 we directly test whether αE-catenin bound to β-catenin in the CCC is sufficient to induce intercellular adhesion, and results from this work show that both junctional monomer and cytosolic homodimer pools of αE-catenin act together to induce strong cell-cell adhesion. However, understanding the specific function of the αE-catenin homodimer and its role in locally controlling actin dynamics at cell-cell junctions has been technically challenging because the N-terminus of αE-catenin mediates both homodimerization and β-catenin binding. Thus, removing the homodimerization domain of αE-catenin also disrupts αE-catenin binding to β-catenin in the CCC. Chapter 3 describes the design of a locked-monomer αE-catenin mutant that uncouples homodimerization from αE-catenin binding to β-catenin. Expression of this mutant in an αE-catenin-/- generated cell line, we show that the αE-catenin homodimer pool is essential for regulation of epithelial intercellular adhesion and cell migration. Finally, in Chapter 4, we identify a link between the AJ complex and the microtubule cytoskeleton in mitosis. Epithelia cells divide parallel to the epithelial plane in order to maintain tissue architecture. Although E-cadherin has been implicated in this, the underlying molecular mechanism remains unclear, and here we identify how E-cadherin is linked to the mitotic spindle in order to instruct the orientation of cell division.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Bianchini, Julie Marie |
|---|---|
| Associated with | Stanford University, Department of Biology. |
| Primary advisor | Nelson, William |
| Thesis advisor | Nelson, William |
| Thesis advisor | Kopito, Ron Rieger |
| Thesis advisor | Theriot, Julie |
| Thesis advisor | Weis, William I |
| Advisor | Kopito, Ron Rieger |
| Advisor | Theriot, Julie |
| Advisor | Weis, William I |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Julie Marie Bianchini. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Julie Marie Bianchini
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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