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AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP.

Cell reports | 2018

Ca2+-permeable AMPA-type glutamate receptors (CP-AMPARs) containing GluA1 but lacking GluA2 subunits contribute to multiple forms of synaptic plasticity, including long-term potentiation (LTP), but mechanisms regulating CP-AMPARs are poorly understood. A-kinase anchoring protein (AKAP) 150 scaffolds kinases and phosphatases to regulate GluA1 phosphorylation and trafficking, and trafficking of AKAP150 itself is modulated by palmitoylation on two Cys residues. Here, we developed a palmitoylation-deficient knockin mouse to show that AKAP150 palmitoylation regulates CP-AMPAR incorporation at hippocampal synapses. Using biochemical, super-resolution imaging, and electrophysiological approaches, we found that palmitoylation promotes AKAP150 localization to recycling endosomes and the postsynaptic density (PSD) to limit CP-AMPAR basal synaptic incorporation. In addition, we found that AKAP150 palmitoylation is required for LTP induced by weaker stimulation that recruits CP-AMPARs to synapses but not stronger stimulation that recruits GluA2-containing AMPARs. Thus, AKAP150 palmitoylation controls its subcellular localization to maintain proper basal and activity-dependent regulation of synaptic AMPAR subunit composition.

Pubmed ID: 30355502 RIS Download

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: P30 NS048154
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS096815
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007635
  • Agency: NIMH NIH HHS, United States
    Id: R00 MH103531
  • Agency: NCRR NIH HHS, United States
    Id: S10 RR023381
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS040701
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001082

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