title: Tyrosine dephosphorylation regulates AMPAR internalisation in mGluR-LTD.
abstract: Long-term depression (LTD) can be induced at hippocampal CA1 synapses by activation of either NMDA receptors (NMDARs) or group I metabotropic glutamate receptors (mGluRs), using their selective agonists NMDA and (RS)-3,5-dihydroxyphenylglycine (DHPG), respectively. Recent studies revealed that DHPG-LTD is dependent on activation of postsynaptic protein tyrosine phosphatases (PTPs), which transiently dephosphorylate tyrosine residues in AMPA receptors (AMPARs). Here we show that while both endogenous GluR2 and GluR3 AMPAR subunits are tyrosine phosphorylated at basal activity, only GluR2 is dephosphorylated in DHPG-LTD. The tyrosine dephosphorylation of GluR2 does not occur in NMDA-LTD. Conversely, while NMDA-LTD is associated with the dephosphorylation of GluR1-serine-845, DHPG-LTD does not alter the phosphorylation of this site. The increased AMPAR endocytosis in DHPG-LTD is PTP-dependent and involves tyrosine dephosphorylation of cell surface AMPARs. Together, these results indicate that the subunit selective tyrosine dephosphorylation of surface GluR2 regulates AMPAR internalisation in DHPG-LTD but not in NMDA-LTD in the hippocampus.
authors.affiliation: Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, School of Medical Sciences, University Walk, Bristol BS81TD, UK.
authors.forename: Clare M
authors.initials: CM
authors.lastname: Gladding
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Collett
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.forename: Zafar I
authors.initials: ZI
authors.lastname: Bashir
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: Elek
authors.initials: E
authors.lastname: Molnár
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004705:Endocytosis / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000378:metabolism; D010766:Phosphorylation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012118:Resorcinols / Q000378:metabolism; D016415:Sequence Alignment; D013569:Synapses / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D018690:Excitatory Amino Acid Agonists; D021122:Protein Subunits; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D014443:Tyrosine; C079215:3,5-dihydroxyphenylglycine; D016202:N-Methylaspartate; D005998:Glycine