Regulation of desmosomal gene expression in human skin cells.

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As part of the junctional complex of many cell types, desmosomes are one of the most specialized anchoring junctions. They fulfill many different structural and communicative roles in tissues and are abundant in tissues that experience mechanical stress, such as keratinocytes (skin cells). Previous work has shown that the GTPase RhoA regulates the expression of the desmosomal protein Desmoglein 1 (DG1). Desmoglein 1 (DG1) is a desmosomal protein that is often used as indicator of differentiation in stratified keratinocytes as it controls the expression of other signature proteins of differentiated keratinocytes, and is critical for the ability of keratinocytes to form a proper barrier in the skin. GTPase are proteins that can exist in either a GTP-bound active or GDP-bound inactive state, and this process is regulated by guanine nucleotide exchange factors (GEFs) which activate the GTPase and GTPase activating proteins (GAPs) which inactive the GTPase. This study investigated a subset of Rho GAPs (p190RhoGAP, RacGAP2 and DLC) to determine their role in regulation of desmosome protein expression. We hypothesized that loss of these GAPs will result in higher levels of desmosomal and adherens junction proteins in SCC9 and A431 cells as RhoAGTPase will remain activated upon their absence. My research found that there are inconsistent decreases in two different cell-cell junctional proteins, Desmoplakin and E-cadherin, as a result of p190 RhoGAP knockdown. No other protein concentrations were affected. We therefore conclude that RacGAP2, DLC GAP and p190RhoGAP do not play a major role in regulation of desmosomal protein gene expression. This work is relevant as it illuminates how desmosomal protein production changes when RhoA GTPase signaling is disrupted. In a greater context, this work contributes to the understanding of cell adhesion in skin cells.