Dr Verderio-Edwards is:

Module Leader of Cell Signalling and Cancer and Molecular Genetics of Human Disease Research Seminars organiser for the Biomedical Life and Health Sciences (BLHS) Research Centre UoA A03 Assistant Coordinator of Output subgroup (REF 2014)

transglutaminase, extracellular matrix, syndecan-4, kidney fibrosis

The molecular biology of Transglutaminase-2 in physiopathological conditions

Transglutaminase type 2 (TG2) (EC 2.3.2.13) belongs to an emergent class of proteins with distinct molecular activities that function both inside and outside the cell and transit the plasma membrane by unconventional secretion. TG2 has been implicated in the pathogenesis of many apparently unrelated diseases, such as tissue fibrosis, celiac disease, cancers, neurodegenerative disorders, and type II diabetes. Although capable of different biological activities, overall its expression and activation is believed to occur as a response to tissue injury and / or cell stress. Protein cross-linking is the enzymatic reaction for which TG2 is better known, involving an acyl transfer reaction between the gamma carboxamide group of a peptide-bound Gln residue and the epsilon-amino group of a peptide-bound Lys residue or a primary amino group of a polyamine. TG2 causes additional post-translational modifications among which protein deamidation of Gln residues contributes to the development of disorders caused by gluten sensitivity.

Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis. Scarpellini A, Huang L, Burhan I, Schroeder N, Funck M, Johnson TS, Verderio EA. J Am Soc Nephrol. 2013 Dec 19 (Epub ahead of print) Transglutaminase-2 interaction with heparin: identification of a heparin binding site that regulates cell adhesion to fibronectin-transglutaminase-2 matrix. Lortat-Jacob H, Burhan I, Scarpellini A, Thomas A, Imberty A, Vivès RR, Johnson T, Gutierrez A, Verderio E, J. Biol. Chem., 2012, 287, 18005-18017 A crucial sequence for transglutaminase type 2 extracellular trafficking in renal tubular epithelial cells lies in its N-terminal -sandwich domain. Chou CY, Streets AJ, Watson PF, Huang L, Verderio E, Johnson TS, J. Biol. Chem., 2011, 286, 27825-27835 Simulated environmental criticalities affect transglutaminase of Malus and Corylus pollens having different allergenic potential. Iorio RA, Di Sandro A, Paris R, Pagliarani G, Tartarini S, Ricci G, Serafini-Fracassini D, Verderio E, Del Duca S, Amino Acids, 2011, 42 (2-3), 1007 An extracellular transglutaminase is required in apple pollen tube growth. Di Sandro A, Del Duca, S, Verderio E, Hargreaves A, Bonner P, Griffin M, Iorio R, Scarpellini A, Serafini-Fracassini D, Biochem. J., 2010, 429, 261-271 Heparan sulphate proteoglycans are receptors for the cell-surface trafficking and biological activity of transglutaminase-2. Scarpellini A, Germack R, Lortat-Jacob H, Muramatsu T, Billett E, Johnson T, Verderio E, J. Biol. Chem., 2009, 284, 18411-1842 Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and beta(1) integrin co-signaling Telci D, Wang Z, Li X, Verderio EA, Humphries MJ, Baccarini M, Basaga H, Griffin M, J. Biol. Chem., 2008, 283 (30), 20937-41