Loss of AKAP150 perturbs distinct neuronal processes in mice

Brian J. Tunquist, Naoto Hoshi, Eric S. Guire, Fang Zhang, Karin Mullendorff, Lorene K. Langeberg, Jacob Raber, John D. Scott

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

A-Kinase Anchoring Proteins (AKAPs) ensure the fidelity of second messenger signaling events by directing protein kinases and phosphatases toward their preferred substrates. AKAP150 brings protein kinase A (PKA), the calcium/calmodulin dependent phosphatase PP2B and protein kinase C (PKC) to postsynaptic membranes where they facilitate the phosphorylation dependent modulation of certain ion channels. Immunofluorescence and electrophysiological recordings were combined with behavioral analyses to assess whether removal of AKAP150 by gene targeting in mice changes the signaling environment to affect excitatory and inhibitory neuronal processes. Mislocalization of PKA in AKAP150 null hippocampal neurons alters the bidirectional modulation of postsynaptic AMPA receptors with concomitant changes in synaptic transmission and memory retention. AKAP150 null mice also exhibit deficits in motor coordination and strength that are consistent with a role for the anchoring protein in the cerebellum. Loss of AKAP150 in sympathetic cervical ganglion (SCG) neurons reduces muscarinic suppression of inhibitory M currents and provides these animals with a measure of resistance to seizures induced by the non-selective muscarinic agonist pilocarpine. These studies argue that distinct AKAP150-enzyme complexes regulate context-dependent neuronal signaling events in vivo.

Original languageEnglish (US)
Pages (from-to)12557-12562
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number34
DOIs
StatePublished - Aug 26 2008

Keywords

  • AMPA
  • Behavior
  • KCNQ
  • Knockout

ASJC Scopus subject areas

  • General

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    Tunquist, B. J., Hoshi, N., Guire, E. S., Zhang, F., Mullendorff, K., Langeberg, L. K., Raber, J., & Scott, J. D. (2008). Loss of AKAP150 perturbs distinct neuronal processes in mice. Proceedings of the National Academy of Sciences of the United States of America, 105(34), 12557-12562. https://doi.org/10.1073/pnas.0805922105