Loss of collagen VII is associated with reduced transglutaminase 2 abundance and activity

Area of Science:

• Biochemistry
• Cell Biology
• Dermatology

Background:

• Collagen VII deficiency causes widespread cellular and tissue issues, but molecular mechanisms remain unclear.
• Recessive dystrophic epidermolysis bullosa (RDEB) serves as a model for studying collagen VII absence.
• Understanding these mechanisms is crucial for RDEB pathogenesis.

Purpose of the Study:

• To investigate cellular responses to collagen VII loss using quantitative proteomics.
• To identify molecular players linking cellular phenotypes in RDEB.
• To analyze protein abundance and interaction changes in the absence of collagen VII.

Main Methods:

• Quantitative disease proteomics applied to RDEB models.
• Analysis of cellular protein abundances and protein-protein interactions.
• Focus on collagen VII-dependent differences.

Main Results:

• Absence of collagen VII altered intracellular protein composition and perturbed cell adhesion, protein trafficking, and autophagy.
• Transglutaminase 2 (TGM2) was identified as a collagen VII interaction partner.
• Reduced TGM2 abundance and activity in RDEB correlated with diminished adhesion, impaired autophagy, and reduced extracellular matrix cross-linking.

Conclusions:

• Transglutaminase 2 (TGM2) acts as a molecular link between collagen VII deficiency and cellular phenotypes in RDEB.
• Reduced TGM2 function contributes to impaired cell adhesion, autophagy, and epidermal-dermal integrity in RDEB.
• Targeting TGM2 may offer therapeutic potential for RDEB and related disorders.