Neuroproteomics and the Detection of Regulatory Phosphosites

Protein phosphorylation is a key post-translational modification that controls intracellular signalling in virtually all cell types. In the nervous system, it contributes to the regulation of neuronal signalling and control processes underlying synaptic plasticity and cognitive functions. However, despite its importance, knowledge about phosphoproteins and their phosphosites in the brain remains limited. A pre-requisite for unravelling brain biology and function at the molecular level, are the qualitative and quantitative analyses of protein phosphorylation and its dynamics. These analyses of the phosphoproteome require novel methodologies in addition to traditional biochemical methods. Current phosphoproteomic workflows have reached a level of maturity, which allow for their use in combination with molecular approaches, and their application to the study of higher order brain function and cognitive processes. Neuroproteomics is emerging as an essential new sub-field of the neurosciences. This review focuses on the recent advances in the application of neuroproteomics to the phosphoproteome and discusses the challenges to come.