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Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.

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Title: Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins.
Authors: Tibbo, AJ
Mika, D
Dobi, S
Ling, J
McFall, A
Tejeda, GS
Blair, C
MacLeod, R
MacQuaide, N
Gök, C
Fuller, W
Smith, BO
Smith, GL
Vandecasteele, G
Brand, T
Baillie, GS
Item Type: Journal Article
Abstract: Cyclic AMP is a ubiquitous second messenger used to transduce intracellular signals from a variety of Gs-coupled receptors. Compartmentalisation of protein intermediates within the cAMP signaling pathway underpins receptor-specific responses. The cAMP effector proteins protein-kinase A and EPAC are found in complexes that also contain phosphodiesterases whose presence ensures a coordinated cellular response to receptor activation events. Popeye domain containing (POPDC) proteins are the most recent class of cAMP effectors to be identified and have crucial roles in cardiac pacemaking and conduction. We report the first observation that POPDC proteins exist in complexes with members of the PDE4 family in cardiac myocytes. We show that POPDC1 preferentially binds the PDE4A sub-family via a specificity motif in the PDE4 UCR1 region and that PDE4s bind to the Popeye domain of POPDC1 in a region known to be susceptible to a mutation that causes human disease. Using a cell-permeable disruptor peptide that displaces the POPDC1-PDE4 complex we show that PDE4 activity localized to POPDC1 modulates cycle length of spontaneous Ca2+ transients firing in intact mouse sinoatrial nodes.
Issue Date: Apr-2022
Date of Acceptance: 3-Jan-2022
URI: http://hdl.handle.net/10044/1/93761
DOI: 10.1016/j.yjmcc.2022.01.001
ISSN: 0022-2828
Publisher: Elsevier
Start Page: 86
End Page: 102
Journal / Book Title: Journal of Molecular and Cellular Cardiology
Volume: 165
Copyright Statement: © 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: British Heart Foundation
Funder's Grant Number: PG/19/13/34247
Keywords: Action potential
Cyclic AMP
PDE4
POPDC1
Submitted as preprint on bioRxiv https://www.biorxiv.org/content/10.1101/2020.09.10.290825v1.full
TREK1
Action potential
Cyclic AMP
PDE4
POPDC1
Submitted as preprint on bioRxiv https://www.biorxiv.org/content/10.1101/2020.09.10.290825v1.full
TREK1
1102 Cardiorespiratory Medicine and Haematology
1116 Medical Physiology
Cardiovascular System & Hematology
Publication Status: Published
Conference Place: England
Online Publication Date: 2022-01-06
Appears in Collections:National Heart and Lung Institute



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