Trafficking of GluR2-containing receptors is governed by protein protein interactions that are regulated by phosphorylation events. GluR2 binds NSF and AP2 in the proximal C terminal region and binds PICK and GRIP1/2 in the extreme C terminal region. GluR2 interaction with NSF is necessary to maintain the synaptic levels of GluR2-containing AMPA receptors both at basal levels and under conditions of synaptic activity. GluR2 interaction with GRIP helps anchor AMPA receptors at the synapse. Phosphorylation of GluR2 at S880 disrupts GRIP interaction but allows binding of PICK. PICK is activated by Ca sensitive Protein kinase C (PKC). Under basal conditions, in hippocampal synapse, GluR2-containing AMPA receptors (GluR2/GluR3) constitutively recycle between the synapse and the endosome by endocytosis and exocytosis. GRIP anchors the receptors at the synapse while PICK interaction internalizes the receptors and NSF helps maintain the synaptic receptors. Cerebellar stellate cells mainly contain GluR3 homomers as Ca permeable receptors. The interaction of GluR3 and GRIP is disrupted by PICK interaction by phosphorylation of equivalent of S880 residue in GluR3. Under conditions of repetitive presynaptic activity, there is PICK dependent removal of GluR2-lacking AMPA receptors and selective incorporation of GluR2-containing AMPA receptors at the synapse. The GluR2-containing AMPA receptors are first delivered to the surface by PICK and mobilized to the synapse by NSF dependent mechanism (Liu SJ and Cull-Candy SG Nat Neurosci. 2005 Jun;8(6):768-75

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AP2A1 , AP2A2 , AP2B1 , AP2M1 , AP2S1 , GRIA1 , GRIA2 , GRIA3 , GRIA4 , NSF , PRKCA , PRKCB , PRKCG , TSPAN7 , PICK1 , GRIP1 , GRIP2 ,