Supramolecular signalling complexes in the nervous system.

It is now apparent that multiprotein signalling complexes or "signalling machines" are responsible for orchestrating many complex signalling pathways in the cell. The synapse is a sub-cellular specialisation which transmits and converts patterns of electrical activity into cellular memory. This processing of electrical information is mediated by the protein components of the synapse. The organisation of synaptic proteins has been investigated over the last number of years using proteomic methods and with the application ofbioinformatics; a landscape of modular protein complexes at the synapse is emerging. Many share a common organisation centred on a receptor/channel, a protein scaffold, (in which the signalling molecules are localised) and membrane to cytoskeleton interactions. The use of PDZ-domain based protein scaffolds is a particularly common feature in the construction of neuronal protein complexes and the differential presence of these proteins in complexes can have functional consequences. Here we overview current proteomic methodologies for the analysis of multiprotein complexes. In addition, we describe the characterisation of a number of multiprotein complexes associated with ion channels (NMDAR, P2X7 and Kir2) and GPCRs (5-HT2A/5-HT2C, D2 and mGluR5) and discuss common their common components and organisation.