ArticleAmerican journal of respiratory cell and molecular biology2014
A soluble adenylyl cyclase form targets to axonemes and rescues beat regulation in soluble adenylyl cyclase knockout mice.
Article in American journal of respiratory cell and molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Targeting Soluble Adenylyl Cyclase for On-Demand Contraception.Physiology (Bethesda, Md.) · 2026Review
- Cyclic AMP Rescue of Motility in Sperm Devoid of Soluble Adenylyl Cyclase.International journal of molecular sciences · 2025Article
- The role of soluble adenylyl cyclase in sensing and regulating intracellular pH.Pflugers Archiv : European journal of physiology · 2024Review
- Two novel heterozygousJournal of genetics · 2024Review
- Strategies to safely target widely expressed soluble adenylyl cyclase for contraception.Frontiers in pharmacology · 2022Article
- Bicarbonate, carbon dioxide and pH sensing via mammalian bicarbonate-regulated soluble adenylyl cyclase.Interface focus · 2021Review
- Molecular and biochemical characterization of the bicarbonate-sensing soluble adenylyl cyclase from a bony fish, the rainbow troutInterface focus · 2021Article
- Optimization of lead compounds into on-demand, nonhormonal contraceptives: leveraging a public-private drug discovery institute collaboration†.Biology of reproduction · 2020Article
- The Effects of the Anti-aging Protein Klotho on Mucociliary Clearance.Frontiers in medicine · 2019Article
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments.Journal of cardiovascular development and disease · 2018Review
- Soluble adenylyl cyclase: A novel player in cardiac hypertrophy induced by isoprenaline or pressure overload.PloS one · 2018Article
- Klotho Inhibits Interleukin-8 Secretion from Cystic Fibrosis Airway Epithelia.Scientific reports · 2017Article
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase.Nature chemical biology · 2016Article
- Soluble adenylyl cyclase mediates hydrogen peroxide-induced changes in epithelial barrier function.Respiratory research · 2016Article
- Hydrogen peroxide stimulation of CFTR reveals an Epac-mediated, soluble AC-dependent cAMP amplification pathway common to GPCR signalling.British journal of pharmacology · 2015Article
- Soluble adenylyl cyclase in health and disease.Biochimica et biophysica acta · 2014Review
- The role of soluble adenylyl cyclase in neurite outgrowth.Biochimica et biophysica acta · 2014Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.