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J Mol Neurosci (2012) 46:410419 DOI 10.1007/s12031-011-9601-8
Beta-Actin is a Target for Transglutaminase Activityat Synaptic Endings in Chicken Telencephalic Cell Cultures
Lars Dolge & Karin Aufenvenne & Heiko Traupe &
Werner Baumgartner
Received: 14 June 2011 /Accepted: 13 July 2011 /Published online: 26 July 2011 # Springer Science+Business Media, LLC 2011
Abstract Transglutaminases are Ca2+-dependent enzymes that catalyse the covalent cross-linking of protein-bound glutamine and lysine residues, which can stabilise proteins or protein aggregates. In the brain, elevated expression levels and activity of transglutaminases are known to be linked with several neurodegenerative diseases. However, little is known about the physiological functions of transglutaminases in the central nervous system. In this study, we examined the expression and activity of transglutaminase 1 in chicken telencephalic cell cultures. We observed a cytosolic expression of transglutaminase 1 in telencephalic neurons. However, transglutaminase 1 activity was restricted to synaptic endings. Transglutaminase targets in the cultured cells were characterised via a biotinylation assay and -actin was identified as a substrate. Furthermore, we were able to show that -actin is a target for the activity of recombinant human transglutaminase 1 in vitro. We propose a mechanism where neuronal transglutaminase 1 is activated by synaptic activity-dependent influx of calcium ions and thereupon catalyse the formation of an intramolecular cross-link in -actin, thereby stabilising the actin cytoskeleton against depolymerising effects. In this way, transglutaminase 1 could modulate actin-dependent plasticity events at synaptic endings.
Keywords Transglutaminase . Actin . Synapse . Telencephalon . Cadherin
Introduction
Transglutaminases (TGases) present a family of calcium-dependent cross-linking enzymes, catalysing a transamidation reaction, which links the carboxamide moiety of a protein-bound glutamine residue to a primary amine (Sarkar et al. 1957; Lorand and Graham 2003). If the primary amine is a protein-bound lysine, an intra- or intermolecular -(-glutamyl)lysine isopeptide bond is formed (Pisano et al. 1968). TGases can be found in microorganisms (Kanaji et al. 1993), plants (Serafini-Fracassini and Del Duca 2008), invertebrates (Singh and Mehta 1994) and vertebrates (Sarkar et al. 1957; Puszkin and Raghuraman 1985; Yasueda et al. 1995; Zhang and Masui 1997). In humans, there are nine known members of the TGase family, TGases 1 to 7, factor XIIIa and erythrocyte band 4.2. All members go back to a common ancestor (Grenard et al. 2001), possessing a...