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

Dove J. Keith, Jennifer L. Sanderson, Emily S. Gibson, Kevin M. Woolfrey, Holly R. Robertson, Kyle Olszewski, Rujun Kang, Alaa El-Husseini, Mark L. Dell'Acqua

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

NMDAreceptor-dependent long-term potentiation (LTP) and depression (LTD) are forms of synaptic plasticity underlying learning andmemory that are expressed through increases and decreases, respectively, in dendritic spine size andAMPAreceptor(AMPAR)phosphorylation and postsynaptic localization. The A-kinase anchoring protein 79/150 (AKAP79/150) signaling scaffold regulatesAMPARphosphorylation, channel activity, and endosomal trafficking associated with LTP and LTD. AKAP79/150 is targeted to dendritic spine plasma membranes by an N-terminal polybasicdomainthat binds phosphoinositide lipids, F-actin,andcadherin cell adhesion molecules.However,wedonot 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.

Original languageEnglish (US)
Pages (from-to)7119-7136
Number of pages18
JournalJournal of Neuroscience
Volume32
Issue number21
DOIs
StatePublished - May 23 2012
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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