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AKAP complex regulates Ca 2+ re‐uptake into heart sarcoplasmic reticulum
Author(s) -
Lygren Birgitte,
Carlson Cathrine Rein,
Santamaria Katja,
Lissandron Valentina,
McSorley Theresa,
Litzenberg Jessica,
Lorenz Dorothea,
Wiesner Burkhard,
Rosenthal Walter,
Zaccolo Manuela,
Taskén Kjetil,
Klussmann Enno
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7401081
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , ryanodine receptor 2 , chemistry , medicine , biology , ryanodine receptor
The β‐adrenergic receptor/cyclic AMP/protein kinase A (PKA) signalling pathway regulates heart rate and contractility. Here, we identified a supramolecular complex consisting of the sarcoplasmic reticulum Ca 2+ ‐ATPase (SERCA2), its negative regulator phospholamban (PLN), the A‐kinase anchoring protein AKAP18δ and PKA. We show that AKAP18δ acts as a scaffold that coordinates PKA phosphorylation of PLN and the adrenergic effect on Ca 2+ re‐uptake. Inhibition of the compartmentalization of this cAMP signalling complex by specific molecular disruptors interferes with the phosphorylation of PLN. This prevents the subsequent release of PLN from SERCA2, thereby affecting the Ca 2+ re‐uptake into the sarcoplasmic reticulum induced by adrenergic stimuli.