Neuroproteomics of the Synapse: Subcellular Quantification of Protein Networks and Signaling Dynamics

Abstract

One of the most fascinating features of the brain is its ability to adapt to its surroundings. Synaptic plasticity, the dynamic mechanism of functional and structural alterations in synaptic strength, is essential for brain functioning and underlies a variety of processes such as learning and memory. Although the molecular mechanisms underlying such rapid plasticity are not fully understood, a consensus exists on the important role of proteins. The study of these neuronal proteins using neuroproteomics has increased rapidly in the last decades, and advancements in MS-based proteomics have broadened our understanding of neuroplasticity exponentially. In this review, we discuss the trends in MS-based neuroproteomics for the study of synaptic protein-protein interactions and protein signaling dynamics, with a focus on sample types, different labeling and enrichment approaches, and data analysis and interpretation. We highlight studies from the last 5 years, with a focus on synapse structure, composition, functioning, or signaling and finally discuss some recent developments that could further advance the field of neuroproteomics.

Keywords: bio-orthogonal amino acids; mass spectrometry; neuroproteomics; protein networks; protein translation; proximity-labeling; synapse.