Fig 1.
Structure of the dendritic spine model.
The model contains submembrane and subendosomal compartments, with AMPAR lateral diffusion, endocytosis and exocytosis.
Fig 2.
AMPAR trafficking in the model.
(A) Schematic representation of AMPAR trafficking between the postsynaptic plasma membrane and endosome used in the model. (B) Detailed bidirectional trafficking pathway showing the interactions between AMPARs, GRIP, PICK1 and NSF.
Fig 3.
Interconversion of the AMPAR phosphorylation states in the model.
(AMPApY = GluA2-Y876-phosphorylated AMPA receptor; AMPApS = GluA2-S880-phosphorylated AMPAR). (A) Influence of AMPAR phosphorylation state on GRIP and PICK1 interactions and trafficking during basal and LTD induction conditions. (B) Interactions between AMPAR and GRIP/PICK1, showing the formation of a tripartite complex.
Fig 4.
AMPAR trafficking under basal conditions and during LTD induction.
(Total AMPAR plasma membrane population includes both phosphorylated, at either GluA2-Y876 or GluA2-S880, and unphosphorylated AMPARs.) (A) Effect of PKC and PTPMEG on AMPAR plasma membrane population when exocytosis is blocked. (B) Effect of PTPMEG on LTD induction in the complete model. (C) AMPAR flux across the plasma membrane under basal and LTD induction conditions.
Fig 5.
Effect of PTPMEG on LTD expression.
(Total AMPAR plasma membrane population includes both phosphorylated, at either GluA2-Y876 or GluA2-S880, and unphosphorylated AMPARs.) (A) LTD expression in a PTPMEG-null system. (B) LTD expression in a PTPMEG-active system. (C) Changes in AMPAR phosphorylation state during LTD induction.
Fig 6.
Effect of PP2A inhibition and SFK on LTD expression.
(A) Effect of varying PP2A inhibition on LTD expression. (B) Effect of increased SFK concentration on LTD expression (only 2 concentrations and SFK-null shown–see Table 2 for the complete set of results). (C) LTD expression in a PTPMEG-null, SFK-null system (equivalent to GluA2-Y876F expression in the in vitro system).
Table 1.
Effect of PP2A inhibition on LTD expression.
Table 2.
Effect of SFK concentration on LTD expression.
Table 3.
Summary of simulation results compared to corresponding experimental results.
Table 4.
Model reactions (rate parameters provided in S1 Table).
Table 5.
Sensitivity analysis results (parameters with a sensitivity coefficient of magnitude above 0.1 are emphasised in bold and discussed in the Methods section).