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

[dystrophic epidermolysis bullosa]

Absence of collagen VII leads to widespread cellular and tissue phenotypes . However , the underlying molecular mechanisms are not well understood . To gain insights into cellular responses to loss of collagen VII , we undertook a quantitative disease proteomics approach . By using recessive dystrophic epidermolysis bullosa (RDEB ), a skin blistering disease caused by collagen VII deficiency , as a genetic model , collagen VII-dependent differences in cellular protein abundances and protein-protein interactions were analyzed . Absence of collagen VII led to alterations of intracellular protein compositions and to perturbations in cell adhesion , protein trafficking , and the turnover pathway autophagy . A potential linker of the different cellular phenotypes is transglutaminase 2 (TGM 2 ), a multifunctional enzyme important for protein cross-linking . TGM 2 was identified as a stable interaction partner of collagen VII . In RDEB , both abundance and activity of TGM 2 were reduced , accounting not only for diminished adhesion and perturbed autophagy but also for reduced cross-linking of the extracellular matrix and for decreased epidermal-dermal integrity in RDEB .

Diseases
Validation

Diseases presenting "recessive dystrophic epidermolysis bullosa" symptom

child syndrome

dystrophic epidermolysis bullosa

junctional epidermolysis bullosa

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