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 Ca(2+) 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 Ca(2+) channels has not been elucidated. Here we report that AKAP15 directly interacts with the C-terminal domain of the alpha(1) subunit of Ca(V)1.1 via a leucine zipper (LZ) motif. Disruption of the LZ interaction effectively inhibits voltage-dependent potentiation of L-type Ca(2+) channels in skeletal muscle cells. Our results reveal a novel mechanism whereby anchoring of PKA to Ca(2+) channels via LZ interactions ensures rapid and efficient phosphorylation of Ca(2+) channels in response to local signals such as cAMP and depolarization.
Hulme
Joanne T
JT
Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.
Ahn
Misol
M
Hauschka
Stephen D
SD
Scheuer
Todd
T
Catterall
William A
WA
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020746:Calcium Channels, L-Type / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D016350:Leucine Zippers; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism*; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
D054758:A Kinase Anchor Proteins; C112596:AKAP7 protein, human; D048868:Adaptor Proteins, Signal Transducing; C487791:Akap7 protein, mouse; D020746:Calcium Channels, L-Type; D002352:Carrier Proteins; D008565:Membrane Proteins; D017868:Cyclic AMP-Dependent Protein Kinases