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Wnt11/Fzd7 signaling compartmentalizes AKAP2/PKA to regulate L-type Ca(2+) channel

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Item Type:Preprint
Title:Wnt11/Fzd7 signaling compartmentalizes AKAP2/PKA to regulate L-type Ca(2+) channel
Creators Name:Csalyi, K.D., Rharass, T., Schulz, M., Phan, M.H.Q., Wakula, P., Mhatre, K.N., Plotnick, D., Werdich, A.A., Zauber, H., Sury, M.D., Selbach, M., Heinzel, F.R., Klussmann, E. and Panakova, D.
Abstract:Calcium influx through the voltage-gated L-type calcium channels (LTCC) mediates a wide range of physiological processes from contraction to secretion. Despite extensive research on regulation of LTCC conductance by PKA phosphorylation in response to β-adrenergic stimulation, the science remains incomplete. Here, we show that Wnt11, a non-canonical Wnt ligand, through its G protein-coupled receptor (GPCR) Fzd7 attenuates the LTCC conductance by preventing the proteolytic processing of its C terminus. This is mediated across species by protein kinase A (PKA), which is compartmentalized by A-kinase anchoring proteins (AKAP). Systematic analysis of all AKAP family members revealed AKAP2 anchoring of PKA is central to the Wnt11-dependent regulation of the channel. The identified Wnt11/AKAP2/PKA signalosome is required for heart development, controlling the intercellular electrical coupling in the developing zebrafish heart. Altogether, our data revealed Wnt11/Fzd7 signaling via AKAP2/PKA as a conserved alternative GPCR system regulating Ca(2+) homeostasis.
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:741637
Date:20 August 2019
Official Publication:https://doi.org/10.1101/741637

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