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TY - JOUR AU - Rosenmund, Christian AU - Carr, Daniel W. AU - Bergeson, Susan E. AU - Nilaver, Gajanan AU - Scott, John D. AU - Westbrook, Gary L. PY - 1994 DA - 1994/04/01 TI - Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons JO - Nature SP - 853 EP - 856 VL - 368 IS - 6474 AB - 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 affinity4–6. 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. SN - 1476-4687 UR - https://doi.org/10.1038/368853a0 DO - 10.1038/368853a0 ID - Rosenmund1994 ER -