High throughput protein expression screening in the nervous system--needs and limitations.

The cellular complexity of the brain (some estimate that there are up to 10(3) different cell types) is exceeded by the synaptic complexity, with each of the approximately 10(11) neurons in the brain having around 10(3)-10(4) synapses. Proteomic studies of the synapse have revealed that the postsynaptic density is the most complex multiprotein structure yet identified, with approximately 10(3) different proteins. Such studies, however, use brain tissue with many different regions and therefore different cell types, and there is clear potential for heterogeneity of protein content at different synapses within and between brain regions. Although large-scale mRNA-based assays are in progress to map this sort of complexity at the cellular level, and indeed all brain-expressed genes, analysis of protein distribution (at synapses and other structures) is still in the very early stages. We review existing large-scale protein expression studies and the specific technical obstacles that need to be overcome before applying the scaling used in nucleic acid based approaches.