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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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