- University of Hamburg - Faculty of Biology - Biocenter Klein Flottbek

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Glutamate receptors

Proper working of a nervous system requires a carefully tuned communication between cells. On one hand there is the necessity to acquire external signals and process them for proper reactions both of single cells and the organism as a whole. On the other side an overall homeostasis must be guaranteed for long term survival (in the genetically determined fashion) as well as for memory function.

Signals - chemical or physical - are extracellular, but the interior of the cell has to react to the signal. This implies the necessity of a signal transduction pathway across the cell's membrane. Signal substances - e. g. neurotransmitters like glutamate - don't enter the cells, but react with receptors on the cell's surface. The receptors are coupled to effectors

An example for the first type is an extracellular receptor combined with a transmembrane pore where the throughput of a second messenger is regulated. A case for this is the ionotropic glutamate receptor containing a cation-specific ion channel.

The other construction principle is that of the metabotropic receptors. Here membraneous receptors associate with G-proteins acting as transducers and signal amplifiers. The third component is a functional protein bringing about the necessary changes of second messenger concentration.

From both an ionotropic (AMPA-sensitive) glutamate receptor and a metabotropic glutamate receptor the structures of the ligand binding domains could be elucidated in the presence and absence of glutamate or inhibitors.

Ionotropic Glutamate Receptor
(exramembraneous domain)
Metabotropic Glutamate Receptor
(extracellular ligand-binding part)
structural details structural details

To make a synapse work, another component is neccessary. A surplus of the transmitter has to be removed from the space between the pre-synaptic nerve terminal (which released the glutamate) and the post-synaptic cell, else the excitation may last for unwanted periods. The depletion of glutamate is performed by a class of glutamate transporters with unique structural features. To this date no structural data to the atomic level are available yet.

Literature: S Nakanishi, Molecular diversity of glutamate receptors and implications for brain function, Science 258 (1992) 597-603
T Gudermann et al, Functional and structural complexity of signal tranduction via G-protein-coupled receptors, Annu. Rev. Neurosci. 20 (1997) 399-427
DJ Slotboom et al, The structure of glutamate transporters shows channel-like features, FEBS Lett. 492 (2001) 183-186

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