AKAP complex regulates Ca2+ re-uptake into heart sarcoplasmic reticulum

Lygren, B. et al. (2007) AKAP complex regulates Ca2+ re-uptake into heart sarcoplasmic reticulum. EMBO Reports, 8(11), pp. 1061-1067. (doi: 10.1038/sj.embor.7401081) (PMID:17901878) (PMCID:PMC2247390)

Abstract

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 Ca2+‐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 Ca2+ 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 Ca2+ re‐uptake into the sarcoplasmic reticulum induced by adrenergic stimuli.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Mcsorley, Ms Therese and Zaccolo, Professor Manuela
• Authors: Lygren, B., Carlson, C. R., Santamaria, K., Lissandron, V., Mcsorley, T., Litzenberg, J., Lorenz, D., Wiesner, B., Rosenthal, W., Zaccolo, M., Taskén, K., and Klussmann, E.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: EMBO Reports
• Publisher: EMBO Press
• ISSN: 1469-221X
• ISSN (Online): 1469-3178