Trafficking of L-type Calcium Channels Mediated by the Postsynaptic Scaffolding Protein AKAP79

• Published in: The Journal of biological chemistry Vol. 277; no. 37; pp. 33598 - 33603
• Main Authors: Altier, Christophe, Dubel, Stefan J., Barrère, Christian, Jarvis, Scott E., Stotz, Steáphanie C., Spaetgens, Reneáe L., Scott, John D., Cornet, Veáronique, De Waard, Michel, Zamponi, Gerald W., Nargeot, Joe¨l, Bourinet, Emmanuel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.09.2002; American Society for Biochemistry and Molecular Biology
• Subjects: A Kinase Anchor Proteins; Adaptor Proteins, Signal Transducing; Amino Acid Motifs; Amino Acid Sequence; Biological Transport; Calcium Channels, L-Type - analysis; Calcium Channels, L-Type - chemistry; Calcium Channels, L-Type - metabolism; Carrier Proteins - physiology; Hemagglutinins; Humans; Molecular Sequence Data
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M202476200

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 β2-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.