D. Aeschlimann et V. Thomazy, Protein crosslinking in assembly and remodelling of extracellular matrices: The role of transglutaminases, CONNECT TIS, 41(1), 2000, pp. 1
Transglutaminases form a family of proteins that have evolved for specializ
ed functions such as protein crosslinking in haemostasis, semen coagulation
, or keratinocyte cornified envelope formation. In contrast to the other me
mbers of this protein family, tissue transglutaminase is a multifunctional
enzyme apparently involved in very disparate biological processes. By virtu
e of its reciprocal Ca2+-dependent crosslinking activity or GTP-dependent s
ignal transducing activity, tissue transglutaminase exhibits true multifunc
tionality at the molecular level, The crosslinking activity can subserve di
sparate biological phenomena depending on the location of the target protei
ns. Intracellular activation of tissue transglutaminase can give rise to cr
osslinked protein envelopes in apoptotic cells, whereas estracellular activ
ation contributes to stabilization of the extracellular matrix and promotes
cell-substrate interaction. While tissue transglutaminase synthesis and ac
tivation is normally part of a protective cellular response contributing to
tissue homeostasis, the enzyme has also been implicated in a number of pat
hological conditions including fibrosis, artherosclerosis, neurodegenerativ
e diseases, celiac disease, and cancer metastasis, This review discusses th
e role of transglutaminases in estracellular matrix crosslinking with a foc
us on the multifunctional enzyme tissue transglutaminase.