Trafficking of L-type calcium channels mediated by the postsynaptic scaffolding protein AKAP79.
Accurate calcium signaling requires spatial and temporal coordination of voltage-gated calcium channels (VGCCs) and a variety of signal transduction proteins. Accordingly, regulation of L-type VGCCs involves the assembly of complexes that include the channel subunits, protein kinase A (PKA), protein kinase A anchoring proteins (AKAPs), and beta2-adrenergic receptors, although the molecular details underlying these interactions remain enigmatic. We show here, by combining extracellular epitope splicing into the channel pore-forming subunit and immunoassays with whole cell and single channel electrophysiological recordings, that AKAP79 directly regulates cell surface expression of L-type calcium channels independently of PKA. This regulation involves a short polyproline sequence contained specifically within the II-III cytoplasmic loop of the channel. Thus we propose a novel mechanism whereby AKAP79 and L-type VGCCs function as components of a biosynthetic mechanism that favors membrane incorporation of organized molecular complexes in a manner that is independent of PKA phosphorylation events.
Altier
Christophe
C
Physiopathologie des Canaux Ioniques, Institut de Génétique Humaine CNRS UPR1142, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France.
Dubel
Stefan J
SJ
Barrère
Christian
C
Jarvis
Scott E
SE
Stotz
Stéphanie C
SC
Spaetgens
Renée L
RL
Scott
John D
JD
Cornet
Véronique
V
De Waard
Michel
M
Zamponi
Gerald W
GW
Nargeot
Joël
J
Bourinet
Emmanuel
E
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001692:Biological Transport; D020746:Calcium Channels, L-Type / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology*; D006388:Hemagglutinins; D006801:Humans; D008969:Molecular Sequence Data
D054758:A Kinase Anchor Proteins; C487775:AKAP5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D020746:Calcium Channels, L-Type; D002352:Carrier Proteins; D006388:Hemagglutinins; C419385:L-type calcium channel alpha(1C)