Reduced PTPRD expression differentially alters brain phosphotyrosine phosphoproteomic profiles of 2 and 12 month-old mice

The receptor type protein tyrosine phosphatase PTPRD is implicated in maturation of synapses of expressing neurons, vulnerability to addictions, reward from addictive substances, vulnerability to restless leg syndrome and densities of neurofibrillary pathology in Alzheimers disease brains by a variety of evidence. However, PTPRDs physiological substrates and adaptations to differences in levels of PTPRD expression in brains of young and aging animals have not been explored in depth. We report phosphoproteomic studies of brains of young and aged mice with different levels of PTPRD expression, gene ontology studies of genes identified in this way and validation of several candidate PTPRD substrates with in vitro assays using recombinant PTPRD phosphatase. PTPRD is well positioned to modulate the extent of phosphorylation of phosphotyrosine phosphoprotein substrates, including those involved in synaptic maturation and adaptation.