Characterisation of a novel transglutaminase, TGase 6, and determination of its expression pattern

• Main Author: Thomas, Helen Ann
• Published: Cardiff University 2004
• Subjects: 572.7
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.583440

Transglutaminases represent a family of enzymes capable of stabilising protein assemblies by y-glutamyl-e-lysine crosslinks. These enzymes catalyse a calcium-dependent transferase reaction between the y-carboxamide group of a peptide-bound glutamine residue and primary amines, most commonly the e-amino group of lysine residues. Eight different transglutaminase gene products have previously been characterised in man, and found to have specialised in the crosslinking of proteins in different biological processes. Identification of a gene cluster on mouse chromosome 2 and analysis of the homologous chromosomal sequences on human chromosome 20ql 1 revealed the presence of a novel gene, TGM6, located upstream from the gene encoding transglutaminase 3. A corresponding gene product, transglutaminase 6 could be identified in a small lung carcinoma cell line, called H69, demonstrating that this was a functional gene. The gene product in human and mouse was subsequently characterised by determining its primary structure and deduced amino acid sequence. This revealed the existence of several splice variants. Analysis of its expression on a RNA and protein level using in situ hybridisation and immunohistochemistry revealed that transglutaminase 6 is expressed predominantly in the central nervous system but also in a number of other tissues, for example, in the epidermis of skin, in the developing vertebrae and other long bones, and in the retinal cells of the eye. Expression was also detected in the brain, particularly in the neuronal cells of the cerebral cortex and the Purkinje cells of the cerebellum. The expression in the cerebral cortex correlated with neurogenesis during development. Transglutaminase activity has been implicated in the formation of aberrant protein complexes in the central nervous system resulting in nerve cell degeneration, for example, in Alzheimer's disease and Huntington's disease. Based on its expression pattern, transglutaminase 6 is a possible candidate to generate the underlying transglutaminase-related pathological changes.