Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons

Christian Rosenmund, Daniel Carr, Susan E. Bergeson, Gajanan Nilaver, John D. Scott, Gary Westbrook

Research output: Contribution to journalArticle

311 Citations (Scopus)

Abstract

Phosphorylation of molecules involved in synaptic transmission by multifunctional protein kinases modulates both pre- and postsynaptic events in the central nervous system. The positioning of kinases near their substrates may be an important part of the regulatory mechanism. The A-kinase-anchoring proteins (AKAPs) are known to bind the regulatory subunit of cyclic AMP-dependent protein kinase A with nanomolar affinity. Here we show that anchoring of protein kinase A by AKAPs is required for the modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate channels. Intracellular perfusion of cultured hippocampal neurons with peptides derived from the conserved kinase binding region of AKAPs prevented the protein kinase A-mediated regulation of AMPA/kainate currents as well as fast excitatory synaptic currents. This effect could be overcome by adding the purified catalytic subunit of protein kinase. A control peptide lacking kinase-binding activity had no effect. To our knowledge, these results provide the first evidence that anchoring of protein kinase A is crucial in the regulation of synaptic function.

Original languageEnglish (US)
Pages (from-to)853-856
Number of pages4
JournalNature
Volume368
Issue number6474
DOIs
StatePublished - Apr 28 1994

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Kainic Acid Receptors
AMPA Receptors
Cyclic AMP-Dependent Protein Kinases
Protein Kinases
Neurons
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Phosphotransferases
Kainic Acid
Peptides
Synaptic Transmission
Catalytic Domain
Central Nervous System
Perfusion
Phosphorylation
Acids

ASJC Scopus subject areas

  • General

Cite this

Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons. / Rosenmund, Christian; Carr, Daniel; Bergeson, Susan E.; Nilaver, Gajanan; Scott, John D.; Westbrook, Gary.

In: Nature, Vol. 368, No. 6474, 28.04.1994, p. 853-856.

Research output: Contribution to journalArticle

Rosenmund, Christian ; Carr, Daniel ; Bergeson, Susan E. ; Nilaver, Gajanan ; Scott, John D. ; Westbrook, Gary. / Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons. In: Nature. 1994 ; Vol. 368, No. 6474. pp. 853-856.
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AU - Westbrook, Gary

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