Stoichiometry of the AMPA receptor´s assembly with regulatory membrane proteins

• Applicant: Dr. Maximilian Ulbrich
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 218662598

The function and transport of the AMPA receptor (AMPAR), the main excitatory neurotransmitter receptor in the brain, are modulated by various mechanisms and proteins. The most studied class of direct AMPAR interactors is the TARP family, and other AMPAR interactors have just recently been discovered, e.g. CNIH-2/3. The assembly with auxiliary subunits has an essential influence on the receptor's physiological properties, but there is still little known about the underlying mechanisms. Using a single molecule fluorescence technique that allows direct observation of membrane proteins in living Xenopus oocytes, we had discovered that different TARPs assemble with AMPARs in variable stoichiometries. In the proposed work, we will use an extended range of single molecule and biochemical techniques to analyze the stoichiometry of AMPARs, TARPs and CNIHs in heterologous systems and cultured neurons from rat hippocampus. We also want to decipher TARP/CNIH interactions with heteromeric AMPAR cores and other modulatory proteins. Finally, we are interested in the molecular determinants of the interactions between the auxiliary subunits and AMPARs. Determination of TARP and CNIH distribution on a cellular and sub-cellular level will help to interpret these results.

• DFG Programme: Research Grants
• Major Instrumentation: Multi-Laser-Box
• Instrumentation Group: 5080 Optisches Mikroskopzubehör