Cited by 108Neuroscience and Neuropharmacology ResearchCellular transport and secretionProtein Kinase Regulation and GTPase Signaling

Palmitoylation of A-Kinase Anchoring Protein 79/150 Regulates Dendritic Endosomal Targeting and Synaptic Plasticity Mechanisms

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Keith, Dove J., Sanderson, Jennifer L., Gibson, Emily S., Woolfrey, Kevin M., Robertson, Holly R., Olszewski, Kyle, Kang, Rujun, El-Husseini, Alaa +1 more·2012·The Journal of Neuroscience

Abstract

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.

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Crossref · 10.1523/jneurosci.0784-12.2012

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  1. Malenka RC Bear MF LTP and LTD: an embarrassment of riches. Neuron 2004 44 5 21 15450156

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Authors
Keith, D. J., Sanderson, J. L., Gibson, E. S., Woolfrey, K. M., Robertson, H. R., Olszewski, K., Kang, R., El-Husseini, A., & Dell'Acqua, M. L.
Affiliations
  • University of Colorado Anschutz (US)
  • University of Colorado Denver (US)
  • Massachusetts Institute of Technology (US)
  • University of British Columbia (CA)
Venue
The Journal of Neuroscience
Published
2012-05-23
Volume
32
Issue
21
Pages
7119-7136
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2083102450
Cited by
108
References
65
Citations by year
2026: 4 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 11 · 2018: 11 · 2017: 9 · 2016: 5 · 2015: 9 · 2014: 10 · 2013: 9 · 2012: 2
FWCI
3.95
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • American Heart Association
  • Michael Smith Health Research BC
  • National Institutes of Health (5t32ns007083-27)
  • Anschutz Medical Campus, University of Colorado (P30 NS048154)
  • Canadian Institutes of Health Research (MOP81144, MOP44052, 20R90479, 20R91909)
  • National Institute on Alcohol Abuse and Alcoholism (T32AA007464)
  • National Institute of General Medical Sciences (T32GM007635)
  • National Institute of Neurological Disorders and Stroke (P30NS048154, T32-NS-007083, R01NS040701)
  • National Center for Research Resources (UL1RR025780)
  • National Center for Complementary and Integrative Health (T32AT002688)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
AKAP79/150, palmitoylation, long-term depression, synaptic plasticity, AMPA receptor trafficking, endosomal recycling, lipid rafts, Rab11, seizure activity, hippocampal neurons, polybasic domain, postsynaptic signaling
MeSH terms
Animals, Cells, Cultured, Chlorocebus aethiops, Dendrites, Female, Hippocampus, Kainic Acid, Male, Neuronal Plasticity, Endosomes, Seizures, Rats, Sprague-Dawley, Rats, Wistar, Long-Term Potentiation, Receptors, AMPA, COS Cells, Protein Transport, Long-Term Synaptic Depression, Dendritic Spines, Rats, A Kinase Anchor Proteins, Lipoylation, Gene Knockdown Techniques

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