Stable synaptic retention of serine-880-phosphorylated GluR2 in hippocampal neurons.
Phosphorylation of S880 within the GluR2 C-terminus has been reported to promote endocytosis of AMPA receptors (AMPARs) by preventing GluR2 interaction with the putative synaptic anchoring proteins GRIP and ABP. It is not yet established however, whether S880 phosphorylation induces removal of AMPARs from synaptic sites, and the trafficking of phosphorylated GluR2 subunits with surface and endocytosed GluR2 has not been directly compared within the same intact neurons. Here we show that phosphorylation of GluR2 subunits by PKC activated with phorbol esters is compartmentally restricted to receptors located at the cell surface. Endogenous AMPARs containing S880-phosphorylated GluR2 remained highly synaptic and colocalized with postsynaptic markers to the same extent as AMPARs which did not contain S880-phosphorylated GluR2. Moreover, following S880 phosphorylation, exogenous GluR2 homomers were found specifically at the cell surface and did not co-traffic with the internalized endosomal GluR2 population. We also show that GluR2 is endogenously phosphorylated by a constitutively active kinase pharmacologically related to PKC, and this phosphorylation is opposed by the protein phosphatase PP1. Our results demonstrate a population of hippocampal AMPARs which do not require interaction with GRIP/ABP for synaptic anchorage.
States
Bradley A
BA
Department of Biochemistry, NYU School of Medicine, NY, USA. bradley_states@sd.vrtx.com
Khatri
Latika
L
Ziff
Edward B
EB
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D016296:Mutagenesis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D000074407:SAP90-PSD95 Associated Proteins; D012694:Serine / Q000378:metabolism; D012845:Sindbis Virus; D013569:Synapses / Q000378:metabolism*; D014162:Transfection
D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; D000074407:SAP90-PSD95 Associated Proteins; D012694:Serine; D011493:Protein Kinase C; C104722:glutamate receptor ionotropic, AMPA 2