Receptor protein tyrosine phosphatase σ binds to neurons in the adult mouse brain

The role of type IIA receptor protein tyrosine phosphatases (RPTPs), which includes LAR, RFTP sigma and RPTP delta, in the nervous system is becoming increasingly recognized. Evidence supports a significant role for these RFTPs during the development of the nervous system as well as after injury, and mutations in RPTPs are associated with human disease. However, a major open question is the nature of the ligands that interact with type IIA RPTPs in the adult brain. Candidates include several different proteins as well as the glycosaminoglycan chains of proteoglycans. In order to investigate this problem, we used a receptor affinity probe assay with RPTP sigma-AP fusion proteins on sections of adult mouse brain and to cultured neurons. Our results demonstrate that the major binding sites for RPTP sigma in adult mouse brain are on neurons and are not proteoglycan GAG chains, as RPTP sigma binding overlaps with the neuronal marker NeuN and was not significantly altered by treatments which eliminate chondroitin sulfate, heparan sulfate, or both. We also demonstrate no overlap of binding of RPTP sigma with perineuronal nets, and a unique modulation of RPTP sigma binding to brain by divalent cations. Our data therefore point to neuronal proteins, rather than CSPGs, as being the ligands for RPTP sigma in the adult, uninjured brain. Published by Elsevier Inc.