Subcellular localization of the 52,000 molecular weight major postsynaptic density protein

We have recently reported that in isolated synaptic junctions, the quantity of the major post-synaptic density protein (mPSDp, Mr = 52,000) increases approximately twenty-fold during the third and fourth weeks of postnatal development. In the study that follows, systematic analyses were carried out to determine the subcellular localization of this prominent synaptic protein in adult brain and non-neuronal tissues. Subcellular fractionation and SDS-gel electrophoresis were used to isolate various tissue components and identify proteins that possessed molecular weights similar to that of the mPSDp. To unambiguously verify the molecular identity of all proteins suspected of being the mPSDp, two-dimensional peptide fingerprinting was carried out. In addition, the different subcellular fractions were examined for the presence of structures morphologically resembling the postsynaptic density. The mPSDp was found only in fractions containing identifiable asymmetric synaptic structures and/or postsynaptic densities. This protein was not found in non-neuronal tissues or any other fraction in which there was not a demonstrable presence of postsynaptic densities. This work strongly indicates that the major PSD protein is a molecular 'marker' specific to asymmetric synapses in the mammalian forebrain.