Molecular Mechanisms of neurotransmitter-mediated signal transduction

1. Signal transduction in glial cells
a) Physiological functions of nucleotide receptors and thrombin receptors
b) Ca2+ -regulation and oscillations

2. Thrombin receptors, PAR-1, PAR-2, and PAR-3, desensitization and turnover

3. Nucleotide receptors (P2Y1 and P2Y2): Expression and analysis of ligand specificity

Protease-activated Receptors (PAR)

Figure: Activation mechanism of PARs

We investigate Thrombin-type proteases as signaling molecules in the brain: the role of protease activated receptors in neuronal damage and in neuroprotection.

Molecular biology research has identified four subtypes of PARs, G protein-coupled receptors, which are named PAR-1 to PAR-4.

Thrombin induces proliferation of brain astrocytes mediated by PARs, which is of significance for reactive astrogliosis. On the other side thrombin has a janus-like action: at high concentration it causes damage of nervous tissue, at very low concentrations which are reached in slightly damaged tissue it plays a specific protective role.

Nucleotide receptors (P2Y)

Figure: Interaction between P2Y2-GFP receptor (green) and clathrin (red fluorescence) 20 min after stimulation with ligand (UTP; 100 µM)

P2 receptors (P2-R), form a large family of membrane proteins that play physiologically important roles in the CNS and the periphery upon binding extracellular ATP.

P2Y receptors (P2Y-Rs), G protein-coupled receptors, are important pharmaceutical targets due to their involvement in the modulation of many tissues and organs.

We aim to elucidate the origin of the P2Y-Rs subtype-selectivity.

Characterization of a high-affinity InsP4 receptor and study of Inositolphosphate metabolism

Figure: Domain structure of p42IP4

1. Biochemical and physiological studies of the function of inositol(1,3,4,5)- tetrakisphosphate and of the high-affinity receptor protein p42IP4

2. Function of InsP4 in neuronal development and in neurodegeneration

Ca2+ regulation in neuroprotection and neurodegeneration in ischemia


Neuronale Schädigungsmechanismen