Post translational Modifications of the Proteome: The Example of Tau in the Neuron and the Brain

In this chapter, we will outline the role that post-translational modifications (PTMs) can play in information processing at the cellular level and at the protein level. These modifications can not only lead to enhanced or decreased activity of a biomolecule, but can also generate novel interaction sites or destroy previously existing ones and thereby change the biomolecule’s position in the network of interactions that characterizes the cell. They can determine, in a direct or indirect manner, the stability of the protein and hence its cellular concentration. In contrast to protein modifications resulting from genomic alterations, the information content of PTMs is inherently dynamic, with a demodifying enzyme class identified for each class of modifying enzymes. The action of these enzymes in the cell is not random, but is tightly regulated through the use of scaffolding proteins that control the spatial proximity of the many enzymes involved in generating a functional outcome of the signal. Understanding this order and how its possible perturbations can lead to disease is a central research effort pursued for various pathologies. An overview of all PTMs linked to disease would require a full encyclopedia that would need updating on an almost daily basis. The importance of novel PTMs is indeed a recurring theme in the present biomedical literature. Novel methodology, especially based on innovative mass spectrometry techniques aimed at getting an unbiased view of all proteome changes that accompany selected diseases, is being developed at a fast pace. In this chapter, we do not aim to present such an enumeration. Rather, trying to “See a World in a Grain of …