LAUSR

First described in the 1950s, tissue tranglutaminase (tTG, transglutaminase 2), is a unique multifunctional member of the transglutaminase family with effects that extend beyond its enzymatic actions. A recently published study demonstrates an important role for endogenous tTG in the pathogenesis of pressure overload-induced heart failure, suggesting crosslinking actions that promote diastolic dysfunction, and protective matrix-preserving effects that prevent chamber dilation [1]. The functions of tTG in the failing heart may involve both enzymatic and nonenzymatic effects with several different cellular targets and a wide range of molecular interactions. Ca2+-dependent transamidation, the best characterized enzymatic function of tTG, modifies proteins by crosslinking their reactive carboxamide side chains to primary amines [2]. tTG also exerts enzymatic functions that do not require Ca2+, acting as a GTPase, protein kinase or protein disulfide isomerase, and participates in non-enzymatic interactions with many different proteins, serving adapter and signaling functions both within and outside the cells [3]. In vitro studies have implicated tTG in a wide range of cellular functions, including cell survival, adhesion and migration, cell growth, proliferation, and differentiation [4]. The absence of significant baseline phenotypic abnormalities in mice with global loss of tTG [5] demonstrated that, despite its broad repertoire of presumed cellular functions, tTG does not play a crucial role in maintaining tissue homeostasis. In contrast, a growing body of evidence suggests that tTG is overexpressed and activated following tissue injury, and may regulate pathophysiologic responses. tTG in heart disease