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Transglutaminase 6: A protein associated with central nervous system development and motor function

Thomas, Helen, Beck, Konrad

, Adamczyk, Magdalena

, Aeschlimann, Pascale Corinne, Langley, Martin Simon, Oita, Radu C., Thiebach, Lars, Hils, Martin and Aeschlimann, Daniel

2013. Transglutaminase 6: A protein associated with central nervous system development and motor function. Amino Acids 44 (1) , pp. 161-177. 10.1007/s00726-011-1091-z

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Official URL: http://dx.doi.org/10.1007/s00726-011-1091-z

Abstract

Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second beta-barrel domain in man and a variant with truncated beta-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca(2+) and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca(2+) and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Dentistry Biosciences
Uncontrolled Keywords:	transglutaminase; sequence; structural model; regulation; central nervous system; ataxia
Publisher:	Springer Verlag
ISSN:	0939-4451
Funders:	Arthritis Research UK, Coeliac UK
Date of First Compliant Deposit:	3 June 2016
Last Modified:	05 Jan 2024 08:11
URI:	https://orca.cardiff.ac.uk/id/eprint/16094