Deciphering Spatial Protein-Protein Interactions in Brain Using Proximity Labeling

Abstract

Cellular biomolecular complexes including protein-protein, protein-RNA, and protein-DNA interactions regulate and execute most biological functions. In particular in brain, protein-protein interactions (PPIs) mediate or regulate virtually all nerve cell functions, such as neurotransmission, cell-cell communication, neurogenesis, synaptogenesis, and synaptic plasticity. Perturbations of PPIs in specific subsets of neurons and glia are thought to underly a majority of neurobiological disorders. Therefore, understanding biological functions at a cellular level requires a reasonably complete catalog of all physical interactions between proteins. An enzyme-catalyzed method to biotinylate proximal interacting proteins within 10 to 300 nm of each other is being increasingly used to characterize the spatiotemporal features of complex PPIs in brain. Thus, proximity labeling has emerged recently as a powerful tool to identify proteomes in distinct cell types in brain as well as proteomes and PPIs in structures difficult to isolate, such as the synaptic cleft, axonal projections, or astrocyte-neuron junctions. In this review, we summarize recent advances in proximity labeling methods and their application to neurobiology.

Keywords: biotinylation; neuroproteomics; protein interaction network; protein–protein interactions; proximity labeling.