Brain-derived neurotrophic factor enhances association of protein tyrosinephosphatase PTP1D with the NMDA receptor subunit NR2B in the cortical postsynaptic density

Our recent studies revealed that brain-derived neurotrophic factor (BDNF) r apidly enhances tyrosine phosphorylation and dephosphorylation of the NMDA receptor subunit, NR2B, in the postsynaptic density (PSD), potentially regu lating synaptic plasticity. To explore the molecular mechanisms underlying synaptic NR2B signaling,we examined the protein tyrosine phosphatase, PTP1D ; BDNF reportedly increases association of PTP1D with tyrosine phosphorylat ed proteins in cortical neurons and Pr 12 cells. We now report that PTP1D i s an intrinsic component of the rat cerebrocortical PSD, based on Western b lot analysis using specific anti-PTP1D antibodies. In addition, NR2B was co -immunoprecipitated with PTP1D using anti-NR2B antibodies or anti-PTP1D ant ibodies, indicating physical association of the subunit with PTP1D. Moreove r, treatment of the purified PSD with BDNF for 5 min elicited a two-fold in crease in the association of NR2B with PTP1D. The BDNF action appeared to b e specific, since nerve growth factor, another member of the neurotrophin g ene family, did not alter the association. Finally, an overlay assay reveal ed that BDNF caused a hue-fold increase in binding of blotted PSD NR2B prot eins to PTP1D-SH2 domains, revealing molecular mechanisms mediating the PTP 1D-NR2B binding. Taken together, our results raise the possibility that PTP 1D participates in BDNF-mediated NR2B signaling cascades at the postsynapti c site, thereby regulating synaptic plasticity. (C) 1999 Elsevier Science B .V. All rights reserved.