Correlation profiling of synaptic sub-fraction proteomes of the mouse brain hippocampus, cortex and cerebellum

Synaptic transmission forms the main mode of signaling and information integration in the nervous system. Here, we identified and quantified proteins from three brain regions and five biochemical synapse sub-fractions. We identified around 4500 proteins in total, of which about 2000 proteins each were quantified from microsome, P2 fraction, synaptosome, synaptic membrane, and postsynaptic density (PSD). Correlation profiling using these data sets identified synaptic functional groups and showed enrichment of canonical presynaptic proteins in synaptosome, and canonical postsynaptic proteins in PSD. In addition, we detected profound brain region specific differences in the extent of enrichment for some functionally associated proteins, exemplified by different AMPAR subunits and the large differences in spatial distribution of their potential interactors. Furthermore, we revealed novel PSD proteins PLEKHA5 and ADGRA1, which using super-resolution microscopy on primary neuronal culture were confirmed to reside in the PSD.