Discovery/History
The initial discovery of Epiplakin came from a patient who had a rare autoimmune skin disease that caused blistering at the junction of the epidermis and dermis. After closer examination, scientists saw that the patient's blood had contained autoantibodies that reacted with an unknown protein in the epidermis. [4]
The initial discovery of Epiplakin came from a patient who had a rare autoimmune skin disease that caused blistering at the junction of the epidermis and dermis. After closer examination, scientists saw that the patient's blood had contained autoantibodies that reacted with an unknown protein in the epidermis. In order to identify the protein, researchers had used the patients own autoantibodies as a probe (single-stranded DNA or RNA fragment designed to find and bind to a specific complementary sequence in a biological sample). After screening, the full sequence of the unknown protein had revealed something abnormal. Scientists concluded that instead of seeing the typical plakin structure, the unknown protein was almost entirely made of repeated plakin domains. [4]
Due to its expression mainly happening within epithelial tissues and given its structure, researchers named it Epiplakin. [4]
Structure
To understand the complex structure of Epiplakin, it is important to first understand the structural framework of the plakin family which Epiplakin belongs to. Plakins generally function as cytolinker proteins, which are structural molecules that connect different cytoskeletal networks together. Some examples are actin and intermediate filaments, microtubules etc. They also connect to cell junctions and membrane complexes. By doing so, they are able to provide stability, maintain the shape of cells and withstand stress caused onto tissues. [5] [6] [7]
Plakins are known for having intricate structure. This includes firstly an N-terminus domain that is involved in binding to junction complexes. Then there is the central rod which is the site that enables dimerization while also providing assembly. Another important factor to note about the structure would be the C-terminus that has repeated domains consisting of plakin. These domains help bind to intermediate filaments like keratins or even neurofilaments. [4] [5]
Although Epiplakin is from the plakin family, it differs from the standard plakin blueprint/structure. Its entire coding region is a single long exon that has over 20 kilobase. Due to its enormous size, the weight of the protein comes to about 725 kDa. It consists of a linear array of repeat domains. In humans, there are 13 PRDs (peptide recognition domains). Unlike plakins, Epiplakin's lack the N-terminus domain that contain the actin-binding regions as well as other domains common to plakins. This drew scientists to the conclusion that Epiplakins must be single-chain proteins rather than having that scaffolding structure we typically see in other proteins. [4] [8]
Studies suggest that Epiplakin’s gene (EPPK1) is present in various vertebrate groups (ex. fishes + tetrapods) indicating evolutionary origins found in a common ancestor. However, due to inactive mutations (zero normality to its function) causing disruption, there is a loss of Epiplakin in that specific lineage. While it may serve beneficial functions across a multitude of vertebrates, under certain evolutionary pressures or shifts, it can become dispensable, suggesting it can only be important in certain environments. [8] [4] [9]
An example of this is terrestrial epithelial stress which refers to the physical/environmental issues that epithelial tissues experience in organisms. Epithelial tissues, which refers to the skin (the lining that technically protects the body from outside forces) go through harsh exposure to UV radiation, dehydration from chemicals and sometimes even come in contact with dangerous to moderate pathogens. Epiplakin is a cytolinker protein that binds the IF (intermediate filament) in the skin cells which help organize and stabilize the cytoskeleton as we previously discussed. Under stress, could be stretching, friction, exposure to chemicals or even just the environment, Epiplakin strengthens the keratin networks to prevent any breakage. A role like this helps the epithelial tissues maintain structure balance and stability while also reducing damage/stress. [8] [9]
Clinical significance
Epiplakin was originally identified as a human epidermal autoantigen in a rare autoimmune skin disorder. [13] Its role in maintaining keratin intermediate filament organization suggests that dysregulation of epiplakin expression or function may contribute to epithelial fragility or altered wound-healing responses, as indicated by accelerated wound closure observed in epiplakin-depleted corneal epithelial cells. [10]
Scientists have examined EPPK1 expression in multiple types/forms of cancers (bladder, lung, colon, etc.). Various studies show that altered Epiplakin levels in tumor tissues show correlation with tumor progression pathways. An example of this would be EPPK1 expression/alterations being linked to a downturned progression in lung cancer and sometimes even cervical cancer. Findings like these show Epiplakin almost as a biomarker within the human body and helping researchers make the connections between high levels of this specific gene expression to unknown illnesses or diseases patients might be experiencing. [14]
2. Skin Healing
Although Epiplakin is used as a very helpful tool in clinical practices, it can also be found in other areas outside medicine. An example of this would be when we gets cuts, burns, or even sometimes when we fall and our knees get scraped. What you'll notice is that over the course of maybe 5-12 days, your skin cells will begin to repair themselves and ultimately close up the wound. It is important to note that your skin cells receive help from keratin filaments which hold the cells together, essentially creating a "net" or "rope" to keep the cells strong enough to avoid tears. [15]
Inside those keratin filaments lies Epiplakin which acts as an extra protective barrier, almost as a safety net around the "rope." Epiplakin helps the skin cells complete their job and avoid falling apart due to stress or other outside factors. With the absence of Epiplakin the cells would not be as stable and therefore would tear much faster. In these types of cases, we notice that these wounds will take more time to close and the tissue within them will become more fragile. [15]
This page is based on this
Wikipedia article Text is available under the
CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.
