title: Loss of collagen VII is associated with reduced transglutaminase 2 abundance and activity.
abstract: 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 (TGM2), a multifunctional enzyme important for protein cross-linking. TGM2 was identified as a stable interaction partner of collagen VII. In RDEB, both abundance and activity of TGM2 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.
authors.affiliation: Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany; ZBSA Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Küttner
authors.affiliation: Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mack
authors.affiliation: Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany; ZBSA Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Gretzmeier
authors.affiliation: Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany; ZBSA Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.affiliation: Department of Dermatology, Medical Center-University of Freiburg, Freiburg, Germany; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany; ZBSA Center for Biological Systems Analysis, University of Freiburg, Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany. Electronic address: joern.dengjel@medizin.uni-freiburg.de.
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
mesh_terms: D001343:Autophagy / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D024143:Collagen Type VII / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D020405:Dermis / Q000166:cytology / Q000201:enzymology*; D004789:Enzyme Activation / Q000502:physiology; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology*; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D010641:Phenotype; D061251:Primary Cell Culture; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D020543:Proteome; D011503:Transglutaminases / Q000235:genetics* / Q000378:metabolism*
chemical_list: C569053:COL7A1 protein, human; D024143:Collagen Type VII; D020543:Proteome; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
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