Quantitative in-depth profiling of the postsynaptic density proteome to understand the molecular mechanisms governing synaptic physiology and pathology

© 2017, Springer Science+Business Media LLC. The postsynaptic density (PSD) is a very large protein complex found in excitatory synapses, the most abundant synaptic type in the brain. PSDs contain key proteins to postsynaptic functioning, being closely related to synaptic plasticity and underlying high cognitive abilities such as learning and memory. Biochemical isolation of PSDs has allowed for their profiling by mass spectrometry-based proteomics, revealing it as a highly complex structure containing over 2000 proteins. Genetic studies have found many genes expressed at the PSD as causing neurological as well as mental and behavioral disorders. Understanding the proteomic architecture and dynamics of the PSD is not only key to understand normal brain function but also highly incapacitating human conditions. Here we present easy and robust protocols to isolate PSDs from very little amounts of brain tissue and a mass spectrometry proteomics procedure that allows to identify and quantify over 2000 different PSD proteins in a routinely fashion.