Brain-derived neurotrophic factor enhances association of protein tyrosine phosphatase PTP1D with the NMDA receptor subunit NR2B in the cortical postsynaptic density.
Our recent studies revealed that brain-derived neurotrophic factor (BDNF) rapidly enhances tyrosine phosphorylation and dephosphorylation of the NMDA receptor subunit, NR2B, in the postsynaptic density (PSD), potentially regulating 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 phosphorylated proteins in cortical neurons and PC 12 cells. We now report that PTP1D is an intrinsic component of the rat cerebrocortical PSD, based on Western blot analysis using specific anti-PTP1D antibodies. In addition, NR2B was co-immunoprecipitated with PTP1D using anti-NR2B antibodies or anti-PTP1D antibodies, indicating physical association of the subunit with PTP1D. Moreover, treatment of the purified PSD with BDNF for 5 min elicited a two-fold increase in the association of NR2B with PTP1D. The BDNF action appeared to be specific, since nerve growth factor, another member of the neurotrophin gene family, did not alter the association. Finally, an overlay assay revealed that BDNF caused a two-fold increase in binding of blotted PSD NR2B proteins to PTP1D-SH2 domains, revealing molecular mechanisms mediating the PTP1D-NR2B binding. Taken together, our results raise the possibility that PTP1D participates in BDNF-mediated NR2B signaling cascades at the postsynaptic site, thereby regulating synaptic plasticity.
Lin
S Y
SY
Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA.
Wu
K
K
Len
G W
GW
Xu
J L
JL
Levine
E S
ES
Suen
P C
PC
Mount
H T
HT
Black
I B
IB
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013570:Synaptic Membranes / Q000378:metabolism*; D018909:src Homology Domains
D019208:Brain-Derived Neurotrophic Factor; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases