15: Epidermal and Dermal Adhesion Flashcards
What is the primary function of desmosomes in epithelial tissues?
Desmosomes, also known as Macula Adherens, serve as major cell adhesion junctions in the epidermis, providing structural integrity and mechanical strength to epithelial tissues by anchoring adjacent cells together.
What are the three major categories of desmosomal proteins?
The three major categories of desmosomal proteins are:
-
Desmosomal cadherins
- Desmogleins
- Desmocollins
-
Armadillo family proteins
- Plakoglobin
- Plakophilins
-
Plakins
- Desmoplakin
- Envoplakin
- Periplakin
How do desmosomal cadherins contribute to epithelial adhesion?
Desmosomal cadherins mediate calcium-dependent adhesion in various epithelial tissues and are crucial for maintaining the structural integrity of the epidermis. They are also known to act as autoantigens in conditions like pemphigus.
What is the significance of heterophilic interactions between desmosomal cadherins?
Heterophilic interactions between desmosomal cadherins (Dsg-Dsc) are significant as they likely form the basis of epidermal intercellular adhesion, enhancing the stability and integrity of epithelial layers.
What are the clinical implications of desmoglein 1 in skin diseases?
Desmoglein 1 is targeted in several skin diseases, including:
- Bullous Impetigo
- Staphylococcal Scalded Skin Syndrome (SSSS)
- Inherited ichthyosis in Netherton Syndrome
Pathogenic autoantibodies to Dsg1 are associated with conditions like pemphigus foliaceus and mucocutaneous pemphigus vulgaris.
A patient with pemphigus foliaceus has autoantibodies targeting which desmosomal cadherin?
Pemphigus foliaceus involves autoantibodies targeting Desmoglein 1 (Dsg1).
A patient has a mutation in Desmoglein 1. What conditions might this lead to?
Mutations in Desmoglein 1 can lead to palmoplantar keratoderma (PPK), bullous impetigo, or inherited ichthyosis in Netherton syndrome.
A patient with inherited ichthyosis in Netherton syndrome has a mutation in which desmosomal cadherin?
Inherited ichthyosis in Netherton syndrome is associated with mutations in Desmoglein 1 (Dsg1).
A patient with palmoplantar keratoderma (PPK) has a mutation in which desmosomal cadherin?
Palmoplantar keratoderma (PPK) is associated with mutations in Desmoglein 1 (Dsg1).
A patient with bullous impetigo has a mutation in which desmosomal cadherin?
Bullous impetigo is associated with mutations in Desmoglein 1 (Dsg1).
What are the three major categories of desmosomal proteins and their roles in epithelial tissues?
The three major categories of desmosomal proteins are:
-
Desmosomal cadherins
- Include desmogleins and desmocollins.
- Mediate calcium-dependent adhesion in epithelial tissues.
- Known as autoantigens in diseases like pemphigus.
-
Armadillo family proteins
- Include plakoglobin and plakophilins.
- Play a role in the structural integrity of desmosomes.
-
Plakins
- Include desmoplakin, envoplakin, and periplakin.
- Connect desmosomes to the cytoskeleton, providing mechanical stability.
How do desmosomal cadherins contribute to intercellular adhesion in epithelial tissues?
Desmosomal cadherins contribute to intercellular adhesion through:
- Homophilic interactions (Dsg-Dsg or Dsc-Dsc) which promote adhesion between similar types of cells.
- Heterophilic interactions (Dsg-Dsc) which likely form the basis of epidermal intercellular adhesion, allowing different cell types to adhere to one another effectively.
What are the clinical implications of desmoglein 1 in autoimmune diseases?
Desmoglein 1 is clinically significant due to its role in:
- Being a target in Bullous Impetigo, SSSS, and Inherited ichthyosis in Netherton Syndrome.
- Cleavage by staphylococcal exfoliative toxin, which disrupts adhesion between cells.
- The presence of pathogenic autoantibodies in conditions like Pemphigus foliaceus and mucocutaneous pemphigus vulgaris, leading to blistering skin diseases.
- Autosomal dominant mutations causing haploinsufficiency of Dsg1, resulting in palmoplantar keratoderma (PPK).
What is the role of Desmoglein 2 in arrhythmogenic right ventricular cardiomyopathy (ARVC)?
Desmoglein 2 causes autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) and is not required for epidermal adhesion.
What are the clinical implications of mutations in Desmoglein 4?
Mutations in Desmoglein 4 cause rare autosomal recessive forms of hypotrichosis and monilethrix, indicating its role in hair follicle integrity.
How does Plakophilin contribute to desmosomal stability?
Plakophilin directly binds to desmoplakin and aids in clustering and lateral stability of the desmosomal plaque, which is crucial for cell adhesion.
What is the significance of Plakoglobin in epidermal keratinocytes?
Plakoglobin, also known as γ-catenin, binds to the cytoplasmic tails of desmogleins and desmocollins, playing a key role in adherens junctions in epidermal keratinocytes.
What are the functions of Desmoplakin in desmosomal function?
Desmoplakin provides a major link between keratin filaments and the desmosomal plaque, existing in two RNA splice variants, with Desmoplakin I being required for normal desmosomal function.
What are the consequences of mutations in Plakophilin 2?
Mutations in Plakophilin 2 are the most common cause of autosomal dominant ARVC, highlighting its critical role in cardiac and epidermal integrity.
What is the role of Envoplakin and Periplakin in the epidermis?
Envoplakin and Periplakin are expressed in the superficial layers of the epidermis, contributing to the structural integrity of the skin.
A patient presents with a rare autosomal recessive form of hypotrichosis. Which desmosomal cadherin mutation is most likely responsible?
The mutation in Desmoglein 4 (Dsg4) is most likely responsible for the rare autosomal recessive form of hypotrichosis.
A patient with pemphigus vulgaris has autoantibodies targeting a specific desmosomal cadherin. Which one is it?
The autoantibodies in pemphigus vulgaris target Desmoglein 3 (Dsg3).
A patient with Naxos disease has a mutation in which protein, and what are the associated symptoms?
Naxos disease is caused by a mutation in Plakoglobin (γ-catenin). Symptoms include diffuse palmoplantar keratoderma (PPK), wooly hair, and arrhythmogenic right ventricular cardiomyopathy (ARVC).
A patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) has a mutation in which desmosomal cadherin?
ARVC is associated with mutations in Desmoglein 2 (Dsg2).