title: Beta-actin is a target for transglutaminase activity at synaptic endings in chicken telencephalic cell cultures.
abstract: Transglutaminases are Ca(2+)-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 β-actin was identified as a substrate. Furthermore, we were able to show that β-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 β-actin, thereby stabilising the actin cytoskeleton against depolymerising effects. In this way, transglutaminase 1 could modulate actin-dependent plasticity events at synaptic endings.
authors.affiliation: Department Cellular Neurobionic, Institute for Biology II, RWTH Aachen, Lukasstrasse 1, 52070, Aachen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Dolge
authors.forename: Karin
authors.initials: K
authors.lastname: Aufenvenne
authors.forename: Heiko
authors.initials: H
authors.lastname: Traupe
authors.forename: Werner
authors.initials: W
authors.lastname: Baumgartner
mesh_terms: D000199:Actins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D000588:Amines / Q000494:pharmacology; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000494:pharmacology; D019921:Biotinylation; D002462:Cell Membrane / Q000201:enzymology; D002467:Cell Nucleus / Q000201:enzymology; D002478:Cells, Cultured / Q000648:ultrastructure; D002642:Chick Embryo; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003599:Cytoskeleton / Q000648:ultrastructure; D003600:Cytosol / Q000201:enzymology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000201:enzymology*; D017924:Nucleopolyhedroviruses / Q000235:genetics; D017729:Presynaptic Terminals / Q000201:enzymology; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology; D013045:Species Specificity; D018411:Spodoptera; D013379:Substrate Specificity; D013687:Telencephalon / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*
chemical_list: D000199:Actins; D000588:Amines; D003432:Cross-Linking Reagents; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C076022:5-(biotinamido)pentylamine; D001710:Biotin; D011503:Transglutaminases; C105804:transglutaminase 1