Expression and function of transglutaminase 1 in the brain

The transglutaminases family includes calcium-dependent cross-linking enzymes catalysing a transamidation reaction between a protein-bound glutamine residue and a small primary amine or a protein-bound lysine residue. Transglutaminase 1, a member of this family, is expressed in different epithelial and endothelial tissues. Recently transglutaminase 1 was also identified in the brain. Here its activity was found to be up regulated in correlation with neurodegenerative diseases. However, little is known about the distribution and the function of transglutaminase 1 in the nervous system. The aim of this study was the characterisation of the expression of transglutaminase 1 in the brain and the analysis of transglutaminase activity in neural cell cultures. To investigate the distribution of transglutaminase 1 in the central nervous system, cryostatic slices of mouse brains were immunohistochemically stained against transglutaminase 1 and neuronal, as well as glial markers. Transglutaminase 1 expression was found in scattered astrocytes throughout the cerebral cortex and the cerebellum, in few neurons inside the granular layer of the cerebellum, the caudoputamen and in parts of different fibre tracts, like the corpus callosum and the external capsule. The function of transglutaminase 1 in these cell types remained enigmatic. Transglutaminase 1 was also found in endothelial cells of the brain vascular system and in parts of the ependymal lining of the ventricular system. Transglutaminase 1 is associated with adherens junctions in endothelial and epithelial cells of other tissues. Therefore we assume that the transglutaminase 1 found in the vascular and ventricular system of the brain is also involved in the stabilisation of intercellular junctions. To clarify the role of transglutaminase 1 in the murine brain, a construct for a conditional knock-out mutant of transglutaminase 1 was cloned and successfully transfected into mouse stem cells. Unfortunately the knock-out mouse was not finished in time. To investigate the activity of transglutaminase 1 two primary cell cultures, murine cerebellar granule cells and chicken telencephalic cells were established. Neurons and astrocytes of the granule cell culture were shown to partly express transglutaminase 1, but the enzyme was inactive in this culture. In the telencephalic cultures a membrane bound transglutaminase 1 staining was detected and a transglutaminase activity located in synaptic endings was found. In addition β-actin was found to be a substrate for this synaptic transglutaminase activity. This finding was supported with the expression of a recombinant transglutaminase 1, which was able to cross-link a small primary amine to beta-actin. A model was proposed for the activation of transglutaminase 1 via calcium influx following synaptic activity and for the stabilisation of F-actin through transglutaminase 1 catalysed intramolecular cross-links between glutamine 41 and lysine 50 of beta-actin. In this way transglutaminase 1 could stabilise the morphology of synaptic endings in a neuronal activity dependent fashion.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2010

Author dc:creator

• Dolge, Lars

Contributors dc:contributor

• Baumgartner, Werner

• info:eu-repo/classification/ddc/570
• Neurobiologie
• Gehirn
• Immuncytochemie
• Zellkultur
• Proteinglutamin-Glutamyltransferase <Proteinglutamin-gamma-glutamyltransferase>
• Exzitatorische Synapse
• Biochemie
• Molekularbiologie
• Knockout <Molekulargenetik>
• Körnerzelle
• Maus
• Huhn
• Biowissenschaften, Biologie
• Körnerzellen
• transglutaminase
• brain
• synapse
• granular cells
• chicken
• mouse

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114035%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51782