ABSTRACT
A non-dysmorphic 10 month old female was discovered at surgery to have severe vasculopathy of both the systemic and pulmonary arteries. These findings were confirmed by pathologic examination. Follow-up angiography has confirmed multiple sites of vascular obstruction which appear to be worsening. Angioplasty has only partially relieved these obstructions. The pathology and possible etiology are reviewed.
Subject(s)
Aortic Stenosis, Supravalvular/diagnosis , Aortic Stenosis, Supravalvular/surgery , Peripheral Vascular Diseases/diagnosis , Peripheral Vascular Diseases/surgery , Pulmonary Valve Stenosis/diagnosis , Pulmonary Valve Stenosis/surgery , Aortic Stenosis, Supravalvular/etiology , Constriction, Pathologic/diagnosis , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Female , Humans , Infant , Peripheral Vascular Diseases/etiology , Pulmonary Valve Stenosis/etiologyABSTRACT
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.
