COL17A1 is a gene that provides instructions for producing type XVII collagen, a protein found in the human body. This protein maintains the integrity and stability of certain tissues. While collagens strengthen connective tissues like bone and tendons, type XVII collagen has a specific role.
COL17A1’s Fundamental Role in Skin
Type XVII collagen is a major component of hemidesmosomes. These structures are on the inner surface of the epidermis, the outermost skin layer. They anchor the epidermis to the underlying skin layers, especially the dermis.
Type XVII collagen acts as a transmembrane protein within hemidesmosomes. It connects the epidermal cells’ internal structures to the extracellular matrix. This connection maintains mechanical stability and adhesion between skin layers. It prevents the separation of the epidermis from the dermis, which would lead to blistering.
Type XVII collagen forms from three identical pro-α1(XVII) chains twisting into a triple-stranded procollagen molecule. Procollagen molecules are released from the cell and processed by enzymes into mature type XVII collagen. Mature collagen molecules arrange into long bundles, contributing to the strong adhesion mediated by hemidesmosomes.
Genetic Disorders Arising from COL17A1 Dysfunction
Mutations in the COL17A1 gene can lead to defective or insufficient protein production, causing health consequences. More than 100 different mutations have been identified, which alter the protein’s instructions. These changes reduce the quantity of functional type XVII collagen in the skin.
Without enough functional type XVII collagen, the epidermis weakly attaches to underlying skin layers. Minor trauma, such as rubbing, can cause skin layers to separate, forming painful blisters. This condition is known as Junctional Epidermolysis Bullosa (JEB), a severe inherited blistering skin disorder.
JEB severity varies with the specific COL17A1 gene mutation. Milder forms (JEB generalized intermediate) show blistering limited to hands, feet, knees, and elbows, often improving after infancy. Severe forms (JEB generalized severe) cause widespread blistering from birth, affecting skin and mucous membranes. Complications of severe JEB include malnourishment, slow growth, extensive scarring, and easily bleeding granulation tissue. This tissue increases vulnerability to infections and fluid loss, and its buildup in the airway can cause breathing difficulties.
COL17A1’s Importance in Hair Biology
COL17A1 also functions within hair follicles. It is present in hair follicle stem cells, responsible for hair regeneration and maintenance. COL17A1 helps maintain these stem cells, supporting their self-renewal and differentiation into cell types needed for hair production.
A decline or mutation in COL17A1 within hair follicles impacts hair health and aging. Reduced COL17A1 expression, often due to aging-related DNA damage, contributes to hair follicle stem cell aging. This can lead to hair follicle miniaturization and hair loss. Maintaining COL17A1 levels in hair follicle stem cells can postpone age-related changes in hair follicles and skin. Additionally, reduced COL17A1 can influence hair graying, highlighting its significance in understanding age-related hair changes.