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AKAP79 enables calcineurin to directly suppress protein kinase A activity

Church, TW; Tewatia, P; Hannan, S; Antunes, J; Eriksson, O; Smart, TG; Hellgren Kotaleski, J; (2021) AKAP79 enables calcineurin to directly suppress protein kinase A activity. Elife , 10 , Article e68164. 10.7554/eLife.68164. (In press). Green open access

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Abstract

Interplay between the second messengers cAMP and Ca2+ is a hallmark of dynamic cellular processes. A common motif is the opposition of the Ca2+-sensitive phosphatase calcineurin and the major cAMP receptor, protein kinase A (PKA). Calcineurin dephosphorylates sites primed by PKA to bring about changes including synaptic long-term depression (LTD). AKAP79 supports signaling of this type by anchoring PKA and calcineurin in tandem. In this study, we discovered that AKAP79 increases the rate of calcineurin dephosphorylation of type II PKA regulatory subunits by an order of magnitude. Fluorescent PKA activity reporter assays, supported by kinetic modeling, show how AKAP79-enhanced calcineurin activity enables suppression of PKA without altering cAMP levels by increasing PKA catalytic subunit capture rate. Experiments with hippocampal neurons indicate that this mechanism contributes towards LTD. This non-canonical mode of PKA regulation may underlie many other cellular processes.

Type: Article
Title: AKAP79 enables calcineurin to directly suppress protein kinase A activity
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.68164
Publisher version: https://doi.org/10.7554/eLife.68164
Language: English
Additional information: © 2021, Church et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Keywords: biochemistry, chemical biology, neuroscience, rat
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10136282
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