Proteomics in neuroscience: from protein to network

Abstract

Proteomic tools offer a new platform for studies of complex biological functions involving large numbers and networks of proteins. Intracellular networks of proteins perform key functions in neurons and glia. The unicellular eukaryote Saccharomyces cerevisiae has been the prototype for eukaryotic proteomic studies, and when combined with genomics, microarrays, genetics, and pharmacology, new insights into the integrated function of the cell emerge. The anatomical complexity of the nervous system both in cell types and in the vast number of synapses introduces novel technical and biological issues regarding the subcellular organization of protein networks. Here we will discuss the technology of proteomics and its applications to the nervous system.

Fig. 1.

Schematic of protein interaction networks in a simple cell. a, A simple hypothetical protein interaction map for 100 proteins. Each protein is shown as ablack dot, and connections between pairs of proteins are indicated by single lines. This is a simple adaptation of a 1200 protein interaction map from Schwikowski et al. (2000).b, Functional group interaction map. Because most interactions are between proteins in the same functional class (Schwikowski et al., 2000), it is possible to summarize the map ina to boxes with a functional definition. In this arbitrary example we have connected various boxes, which on the basis of a published yeast interaction study could be: A, Amino acid metabolism; B, protein degradation;C, cell cycle control; D, signal transduction; E, cell polarity; F, vesicular transport; G, cell structure.

Fig. 2.

A hypothetical neuron interaction map.a, A map of a simple spherical cell as shown in Figure1a. b, A map of interactions superimposed on the subcellular architecture of neurons. The soma network is the same as that for the spherical cell, and five individual synapse protein interaction maps are shown. The synapse networks could under many conditions behave autonomously, and under other conditions interact with the soma network. The spatial organization of neuronal architecture will present novel regulatory features as well as pose methodological challenges.