Schloss P. DFG - Deutsche Forschungsgemeinschaft SCHL 353/13-1: Serotonylierung neuronaler Proteine durch Transglutminasen - ein Mechanismus neuronaler Plastizität. 01/2013-12/2015.
Serotonin (5-hydroxytryptamine, 5-HT) was first discovered in the blood serum as a vasoconstrictor substance. Here, 5-HT is also covalently incorporated into distinct proteins involved in thrombus formation. This process is mediated by transglutaminases and has been termed “serotonylation”. In the central nervous system (CNS) 5-HT plays important roles in both embryonic development as a mediator of neurogenesis and in the mature brain as a neurotransmitter. Disturbances in the 5-HT system have also been indicated in several psychiatric disorders, however, it is questionable whether this is only due to 5-HT acting as a classical neurotransmitter. Taking lessons from the fate of 5-HT during thrombin formation in the blood it is conceivable that also in the CNS 5-HT can serve as a substrate for transglutaminases to form cross-linked matrices – a possibility which has not been investigated so far. The major goal of this proposal is to unravel new mechanisms how serotonin can interact with neural proteins to form multivalent cross-links and how such yet unknown processes may contribute to neuronal plasticity.