PROTEIN CROSS-LINKING BY TRANSGLUTAMINASE INDUCED IN LONG-TERM POTENTIATION IN THE CA1 REGION OF HIPPOCAMPAL SLICES

Long-term potentiation induced by high-frequency stimulation of Schaffer collaterals in slices of rat hippocampus is accompanied by protein cross-linking by the Ca2+-dependent enzyme transglutaminase. This conclusion was drawn from the accumulation of the "isodipeptide" epsilon-(gamma-glutamyl)lysine in the proteolytic digests of tetanized, but not of control, slices. The isopeptide bond is formed by transglutaminase between glutamyl-gamma-CONH2 and lysyl-epsilon-NH2 groups of proteins. It is suggested that the Ca2+-induced covalent cross-linking of neuronal, probably dendritic, proteins may be part of the mechanism of long-term plastic changes via stabilization of newly formed supramolecular protein assemblies at the synapse.