Trafficking of L-type calcium channels mediated by the postsynaptic scaffolding protein AKAP79 |
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Authors: | Altier Christophe Dubel Stefan J Barrère Christian Jarvis Scott E Stotz Stéphanie C Spaetgens Renée L Scott John D Cornet Véronique De Waard Michel Zamponi Gerald W Nargeot Joël Bourinet Emmanuel |
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Affiliation: | Physiopathologie des Canaux Ioniques, Institut de Génétique Humaine CNRS UPR1142, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France. |
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Abstract: | 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. |
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