ABSTRACT
Diabetes and psoriasis are prevalent conditions with a spectrum of serious adverse outcomes. Both diseases are common comorbidities for each other, and diabetes is considered as a risk factor for psoriasis and vice versa. However, it is our contention that these diseases are not merely comorbidities of each other but rather share common underlying pathophysiologies (ie, genes and epigenetic changes, inflammation, abnormal environment, and insulin resistance) that drive disease. As such, they can be viewed as facets of the same prism. Genes can cause or permit susceptibility to damage from abnormal external and internal environmental factors, inflammation, and insulin resistance which can also drive epigenetic changes. These co-existing mechanisms act in a vicious cycle over time to potentiate cell and tissue damage to ultimately drive disease. Viewing diabetes and psoriasis through the same prism suggests potential for therapies that could be used to treat both conditions. Although additional controlled trials and research are warranted, we believe that our understanding of the overlapping pathophysiologies continues to grow, so too will our therapeutic options.
ABSTRACT
Quantifying multi-molecular complex assembly in specific cytoplasmic compartments is crucial to understand how cells use assembly/disassembly of these complexes to control function. Currently, biophysical methods like Fluorescence Resonance Energy Transfer and Fluorescence Correlation Spectroscopy provide quantitative measurements of direct protein-protein interactions, while traditional biochemical approaches such as sub-cellular fractionation and immunoprecipitation remain the main approaches used to study multi-protein complex assembly/disassembly dynamics. In this article, we validate and quantify multi-protein adherens junction complex assembly in situ using light microscopy and Fluorescence Covariance Analysis. Utilizing specific fluorescently-labeled protein pairs, we quantified various stages of adherens junction complex assembly, the multiprotein complex regulating epithelial tissue structure and function following de novo cell-cell contact. We demonstrate: minimal cadherin-catenin complex assembly in the perinuclear cytoplasm and subsequent localization to the cell-cell contact zone, assembly of adherens junction complexes, acto-myosin tension-mediated anchoring, and adherens junction maturation following de novo cell-cell contact. Finally applying Fluorescence Covariance Analysis in live cells expressing fluorescently tagged adherens junction complex proteins, we also quantified adherens junction complex assembly dynamics during epithelial monolayer formation.
