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

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

Research output: Contribution to journalArticle

313 Scopus citations

Abstract

Phosphorylation of molecules involved in synaptic transmission by multifunctional protein kinases modulates both pre- and post-synaptic events in the central nervous system1,2. The positioning of kinases near their substrates may be an important part of the regulatory mechanism. The A-kinase-anchoring proteins (AKAPs; ref. 3) are known to bind the regulatory subunit of cyclic AMP-dependent protein kinase A with nanomolar affinity 4-6. Here we show that anchoring of protein kinase A by AKAPs is required for the modulation of α-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid (AMPA)/kainate channels4,5. Intracellular per-fusion 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 - Jan 1 1994

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