More Complex than Expected

Bernd Fakler and Uwe Schulte, members of BIOSS, and their team were able to completely unravel the structure of the most important neurotransmitter receptor in the brain.

The brain is able to take in, process and store information primarily thanks to the function of synapses, the communication interfaces between nerve cells. The transmission of signals at these interfaces occurs via excitatory and inhibitory receptors. Among these, AMPA-type glutamate receptors (AMPARs) are the most prominent in terms of numbers. Prof. Dr. Bernd Fakler and Dr. Uwe Schulte, both members of the BIOSS Cluster of Excellence, and other researchers in the Collaborative Research Centre 746 based at the Institute of Physiology of the University of Freiburg were able to completely unravel the assembly and the architecture of substructures of native AMPA receptors. These findings have now been published in the renowned specialist journal Neuron.

The receptors determine more or less the entire physiology of the cell through synapses controlled by glutamate, which functions as a transmitter. The receptors rebuild and stabilise the cell’s physiology, enable and control the speedy transmission of signals, and adjust the dynamics of synapses to different activities. This latter function is a decisive mechanism for the development of memory and learning processes in the human brain and is therefore extremely important.

Although the AMPA receptors are vital for the brain’s functions, there is still much to discover about these integral membrane proteins. We know that they consist of pore-forming subunits and three types of auxiliary proteins, which together explain the biophysical characteristics of receptors. But we are still completely in the dark when it comes to the molecular structure of the AMPA receptors’ complex cell physiology.

Thanks to new methods of proteomic analysis, the scientists were able to determine that AMPA receptors are assembled from a pool of 34 proteins. The identification of 21 subunit proteins was also a surprising discovery. Either little is known about the function of these proteins, or they have not been associated with excitatory neurotransmitter receptors before now. The findings of the team from the University of Freiburg will enable scientists to analyse the molecular structure and mechanisms of AMPA receptors, which play such a fundamental role in the brain.

                                                                                                              Spectrum of AMPA receptors with
                                                                                                              subunits at the synaptic cleft

Publication:
High-resolution proteomics unravel architecture and full molecular diversity of native AMPA receptor complexes.
Schwenk J, Harmel N, Brechet A, Zolles G, Berkefeld H, Müller CS, Bildl W, Baehrens D, Hüber B, Kulik A, Klöcker N, Schulte U, Fakler B (2012).
Neuron 74, 621-633, (http://dx.doi.org/10.1016/j.neuron.2012.03.034)