Figure 2

The phosphorylation of AMPA receptor subunits and its interaction with partner proteins in spinal neurons. In spinal neurons, it has shown that PKA mediates the phosphorylation of serine at the Serine⁸⁴⁵ site, and PKC targets the Serine⁸³¹ site following noxious stimulation. More specifically, CaMKII mediates the phosphorylation of GluR1 subunit of AMPA receptor at both Serine⁸³¹ and Serine⁸⁴⁵ sites in spinal neurons after strong noxious peripheral stimulation. GluR2 subunits of AMPA receptors may bind to GRIP and PICK1, which play an important role in the GluR2 trafficking. GRIP anchors GluR2 subunits at synapses, whereas PICK1 brings PKC to synaptic GluR2. PKC phosphorylates GluR2 Serine⁸⁸⁰ to release GluR2 from GRIP and to promote GluR2 internalization. CFA-induced peripheral inflammation could induce GluR2 internalization in dorsal horn neurons. Stargazin binds to GluR1, 2, and 4. Binding of the Stargazin C-terminal tail to PSD-95 mediates the synaptic targeting of surface AMPA receptors. SAP 97 binds to the GluR1 C-terminus, interacts with the actin-associated protein 4.1N and is implicated in GluR1 synaptic insertion. NSF protein plays a role in membrane fusion processes and also interacts with GluR2 and GluR3 subunits of AMPA receptors. The following abbreviations are used: PKA, protein kinase A; PKC, protein kinase C; CaMKII, Ca²⁺/calmodulin-dependent protein kinase II; GRIP, glutamate receptor interacting protein; PICK1, protein interacting with C-Kinase; CFA, complete Freund Adjuvant; TARP, transmembrane AMPA receptor regulatory proteins; PDZ, postsynaptic density zone; PSD, postsynaptic density; SAP 97, synapse-associated protein 97; NSF, N-ethylmaleimide sensitive fusion.