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Palmitoylation of A-kinase anchoring protein 79/150 regulates dendritic endosomal targeting and synaptic plasticity mechanisms.

NMDA receptor-dependent long-term potentiation (LTP) and depression (LTD) are forms of synaptic plasticity underlying learning and memory that are expressed through increases and decreases, respectively, in dendritic spine size and AMPA receptor (AMPAR) phosphorylation and postsynaptic localization. The A-kinase anchoring protein 79/150 (AKAP79/150) signaling scaffold regulates AMPAR phosphorylation, channel activity, and endosomal trafficking associated with LTP and LTD. AKAP79/150 is targeted to dendritic spine plasma membranes by an N-terminal polybasic domain that binds phosphoinositide lipids, F-actin, and cadherin cell adhesion molecules. However, we do not understand how regulation of AKAP targeting controls AMPAR endosomal trafficking. Here, we report that palmitoylation of the AKAP N-terminal polybasic domain targets it to postsynaptic lipid rafts and dendritic recycling endosomes. AKAP palmitoylation was regulated by seizure activity in vivo and LTP/LTD plasticity-inducing stimuli in cultured rat hippocampal neurons. With chemical LTP induction, we observed AKAP79 dendritic spine recruitment that required palmityolation and Rab11-regulated endosome recycling coincident with spine enlargement and AMPAR surface delivery. Importantly, a palmitoylation-deficient AKAP79 mutant impaired regulation of spine size, endosome recycling, AMPAR trafficking, and synaptic potentiation. These findings emphasize the emerging importance of palmitoylation in controlling synaptic function and reveal novel roles for the AKAP79/150 signaling complex in dendritic endosomes.

Pubmed ID: 22623657 RIS Download

Mesh terms: A Kinase Anchor Proteins | Animals | COS Cells | Cells, Cultured | Cercopithecus aethiops | Dendrites | Dendritic Spines | Endosomes | Female | Gene Knockdown Techniques | Hippocampus | Kainic Acid | Lipoylation | Long-Term Potentiation | Long-Term Synaptic Depression | Male | Neuronal Plasticity | Protein Transport | Rats | Rats, Sprague-Dawley | Rats, Wistar | Receptors, AMPA | Seizures

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Associated grants

  • Agency: NCRR NIH HHS, Id: UL1 RR025780
  • Agency: NINDS NIH HHS, Id: T32 NS007083
  • Agency: NCCIH NIH HHS, Id: T32AT002688
  • Agency: NIAAA NIH HHS, Id: T32 AA007464
  • Agency: NINDS NIH HHS, Id: P30 NS048154
  • Agency: NINDS NIH HHS, Id: R01NS040701
  • Agency: NIAAA NIH HHS, Id: T32AA007464
  • Agency: NIGMS NIH HHS, Id: T32 GM007635
  • Agency: NIGMS NIH HHS, Id: T32GM007635
  • Agency: NCRR NIH HHS, Id: UL1RR025780
  • Agency: Canadian Institutes of Health Research, Id: 20R90479
  • Agency: NINDS NIH HHS, Id: R01 NS040701
  • Agency: Canadian Institutes of Health Research, Id: 20R91909
  • Agency: Canadian Institutes of Health Research, Id: MOP44052
  • Agency: Canadian Institutes of Health Research, Id: MOP81144
  • Agency: NCCIH NIH HHS, Id: T32 AT002688
  • Agency: NINDS NIH HHS, Id: P30NS048154
  • Agency: NINDS NIH HHS, Id: T32NS007083

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