Dissertation
Nesprin-2G and cell-matrix adhesions influence cell migration during skin wound healing
Doctor of Philosophy (PhD), Washington State University
01/2019
Handle:
https://hdl.handle.net/2376/16733
Abstract
Human skin is essential for separating internal organs from environmental, physical, and biological insults. The skin is composed of two layers, the epidermis and dermis, which are composed of primarily keratinocytes and fibroblasts, respectively. The epidermis prevents water loss and invasion of pathogens while the dermis plays a supportive role and gives skin its stretchy property. Damage to either of these layers initiates wound healing in which the cells of the epidermis and dermis migrate into the area to restore skin function. Wound healing in both layers begins with the infiltration of migrating cells into the wound. Cell migration is mediated by a variety of proteins, including the nucleus, actin cytoskeleton, and cell-matrix adhesions. The nucleus/actin cytoskeleton interaction is important in nuclear positioning and proper orientation during cell migration. Cell-matrix adhesions allow cells to adhere to the underlying matrix and to migrate across this matrix during cell migration. Here, we explore two cell-matrix adhesions: focal adhesions (FAs) and hemidesmosomes (HDs). We show that loss of a nuclear protein, nesprin-2G, leads to an abnormal actin cytoskeleton and FA formation in primary mouse fibroblasts. This loss of FA formation leads to inability of the knockout cells to tug on their underlying matrix to generate traction forces used during cell migration. Consequently, the loss of nesprin-2G results in decreased cell migration compared to wildtype fibroblasts. However, these results are not replicated in keratinocytes. The formation of these adhesions is crucial, but it is also important to understand how these protein components assemble. To better understand this mechanism, we explored the role of the α6 integrin message in α6β4 integrin localization to HDs. We show that a sequence within the 3’ untranslated region (UTR) of the α6 integrin message is required for localization of α6β4 integrin to HDs in A549 cells. Sequences lacking this 3’UTR allow the formation of α6β4 integrin, but it is not localized to HDs. Taken together, these results imply that adhesion formation is a tightly regulated processes which is imperative for cell attachment and migration.
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Details
- Title
- Nesprin-2G and cell-matrix adhesions influence cell migration during skin wound healing
- Creators
- Alexandra Woychek
- Contributors
- Ryan Driskell (Advisor)Jonathan Jones (Advisor)Kwanhee Kim (Committee Member)Michael Konkel (Committee Member)Gary Wayman (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Molecular Biosciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 146
- Identifiers
- 99900581619001842
- Language
- English
- Resource Type
- Dissertation