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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
- either rigidly with both functions implemented by two domains of the same protein
- or by association to other protein groups in the case of three-component transmembrane signaling systems.
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) |
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| 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