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 (CaV1.1) 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 α1 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.