TY - JOUR T1 - Wnt11/Fzd7 signaling compartmentalizes AKAP2/PKA to regulate L-type Ca<sup>2+</sup> channel JF - bioRxiv DO - 10.1101/741637 SP - 741637 AU - Kitti D. Csályi AU - Tareck Rharass AU - Maike Schulz AU - Mai H.Q. Phan AU - Paulina Wakula AU - Ketaki N. Mhatre AU - David Plotnick AU - Andreas A. Werdich AU - Henrik Zauber AU - Matthias D. Sury AU - Matthias Selbach AU - Frank R. Heinzel AU - Enno Klußmann AU - Daniela Panáková Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/20/741637.abstract N2 - 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 Ca2+ homeostasis. ER -