A novel leucine zipper targets AKAP15 and cyclic AMP-dependent protein kinase to the C terminus of the skeletal muscle Ca2+ channel and modulates its function

In skeletal muscle, voltage-dependent potentiation of L-type Ca2+ channel (Ca(V)1.1) activity requires phosphorylation by cyclic AMP-dependent protein kinase (PKA) anchored via an A kinase-anchoring protein (AKAP15). However, the mechanism by which AKAP15 targets PKA to L-type Ca2+ channels has not been elucidated. Here we report that AKAP15 directly interacts with the C-terminal domain of the a, subunit of CaV1.1 via a leucine zipper (LZ) motif. Disruption of the LZ interaction effectively inhibits voltage-dependent potentiation of L-type Ca2+ channels in skeletal muscle cells. Our results reveal a novel mechanism whereby anchoring of PKA to Ca2+ channels via LZ interactions ensures rapid and efficient phosphorylation of Ca2+ channels in response to local signals such as cAMP and depolarization.