Cell Reports
Volume 25, Issue 4, 23 October 2018, Pages 974-987.e4
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Article
AKAP150 Palmitoylation Regulates Synaptic Incorporation of Ca2+-Permeable AMPA Receptors to Control LTP

https://doi.org/10.1016/j.celrep.2018.09.085Get rights and content
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Highlights

  • AKAP150 palmitoylation controls localization to recycling endosomes and the PSD

  • AKAP150 palmitoylation limits basal synaptic incorporation of CP-AMPARs

  • CP-AMPAR synaptic incorporation during LTP depends on induction stimulus

  • AKAP150 palmitoylation is required for CP-AMPAR-dependent LTP

Summary

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.

Keywords

LTP
LTD
calcium-permeable AMPA receptor
AKAP
palmityolation
PKA
calcineurin
PSD

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