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| http://purl.uniprot.org/citations/24874272 | http://www.w3.org/2000/01/rdf-schema#comment | "Ciliary beating is important for effective mucociliary clearance. Soluble adenylyl cyclase (sAC) regulates ciliary beating, and a roughly 50-kD sAC variant is expressed in axonemes. Normal human bronchial epithelial (NHBE) cells express multiple sAC splice variants: full-length sAC; variants with catalytic domain 1 (C1) deletions; and variants with partial C1. One variant, sACex5v2-ex12v2, contains two alternative splices creating new exons 5 (ex5v2) and 12 (ex12v2), encoding a roughly 45-kD protein. It is therefore similar in size to ciliary sAC. The variant increases in expression upon ciliogenesis during differentiation at the air-liquid interface. When expressed in NHBE cells, this variant was targeted to cilia. Exons 5v2-7 were important for ciliary targeting, whereas exons 2-4 prevented it. In vitro, cytoplasmic sACex2-ex12v2 (containing C1 and C2) was the only variant producing cAMP. Ciliary sACex5v2-ex12v2 was not catalytically active. Airway epithelial cells isolated from wild-type mice revealed sAC-dependent ciliary beat frequency (CBF) regulation, analogous to NHBE cells: CBF rescue from HCO3(-)/CO2-mediated intracellular acidification was sensitive to the sAC inhibitor, KH7. Compared with wild type, sAC C2 knockout (KO) mice revealed lower CBF baseline, and the HCO3(-)/CO2-mediated CBF decrease was not inhibited by KH7, confirming lack of functional sAC. Human sACex5v2-ex12v2 was targeted to cilia and sACex2-ex12v2 to the cytoplasm in these KO mice. Introduction of the ciliary sACex5v2-ex12v2 variant, but not the cytoplasmic sACex2-ex12v2, restored functional sAC activity in C2 KO mice. Thus, we show, for the first time, a mammalian axonemal targeting sequence that localizes a sAC variant to cilia to regulate CBF."xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.org/dc/terms/identifier | "doi:10.1165/rcmb.2013-0542oc"xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/author | "Levin L.R."xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/author | "Buck J."xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/author | "Fregien N."xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/author | "Salathe M."xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/author | "Baumlin N."xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/name | "Am J Respir Cell Mol Biol"xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/pages | "750-760"xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/title | "A soluble adenylyl cyclase form targets to axonemes and rescues beat regulation in soluble adenylyl cyclase knockout mice."xsd:string |
| http://purl.uniprot.org/citations/24874272 | http://purl.uniprot.org/core/volume | "51"xsd:string |
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