Tyrosine dephosphorylation regulates AMPAR internalisation in mGluR-LTD

摘要

Long-term depression (LTD) can be induced at hippocampal CAl synapses by activation of either NMDAreceptors (NMDARs) or group I metabotropic glutamate receptors (mGluRs), using their selective agonists NMDAand (RS)-3,5-dihydroxyphenylglycine (DHPG), respectively. Recent studies revealed that DHPG-LTD is dependenton activation of postsynaptic protein tyrosine phosphatases (PTPs), which transiently dephosphorylate tyrosineresidues in AMPA receptors (AMPARs). Here we show that while both endogenous GIuR2 and GIuR3 AMPARsubunits are tyrosine phosphorylated at basal activity, only GIuR2 is dephosphorylated in DHPG-LTD. Thetyrosine dephosphorylation of GIuR2 does not occur in NMDA-LTD. Conversely, while NMDA-LTD is associatedwith the dephosphorylation of GluRl-serine-845, DHPG-LTD does not alter the phosphorylation of this site. Theincreased AMPAR endocytosis in DHPG-LTD is PTP-dependent and involves tyrosine dephosphorylation of cellsurface AMPARs. Together, these results indicate that the subunit selective tyrosine dephosphorylation of surfaceGIuR2 regulates AMPAR internalisation in DHPG-LTD but not in NMDA-LTD in the hippocampus.