NDLI: Soluble Adenylyl Cyclase Is Localized to Cilia and Contributes to Ciliary Beat Frequency Regulation via Production of cAMP

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Soluble Adenylyl Cyclase Is Localized to Cilia and Contributes to Ciliary Beat Frequency Regulation via Production of cAMP

Content Provider	Semantic Scholar
Author	Schmid, Andreas Sutto, Zoltan Nlend, Marie-Christine Horváth, Gábor Schmid, Nathalie Buck, Jochen Levin, Lonny R. Conner, Gregory E. Fregien, Nevis L. Salathe, Matthias A.
Copyright Year	2007
Abstract	Ciliated airway epithelial cells are subject to sustained changes in intracellular CO(2)/HCO(3)(-) during exacerbations of airway diseases, but the role of CO(2)/HCO(3)(-)-sensitive soluble adenylyl cyclase (sAC) in ciliary beat regulation is unknown. We now show not only sAC expression in human airway epithelia (by RT-PCR, Western blotting, and immunofluorescence) but also its specific localization to the axoneme (Western blotting and immunofluorescence). Real time estimations of [cAMP] changes in ciliated cells, using FRET between fluorescently tagged PKA subunits (expressed under the foxj1 promoter solely in ciliated cells), revealed CO(2)/HCO(3)(-)-mediated cAMP production. This cAMP production was specifically blocked by sAC inhibitors but not by transmembrane adenylyl cyclase (tmAC) inhibitors. In addition, this cAMP production stimulated ciliary beat frequency (CBF) independently of intracellular pH because PKA and sAC inhibitors were uniquely able to block CO(2)/HCO(3)(-)-mediated changes in CBF (while tmAC inhibitors had no effect). Thus, sAC is localized to motile airway cilia and it contributes to the regulation of human airway CBF. In addition, CO(2)/HCO(3)(-) increases indeed reversibly stimulate intracellular cAMP production by sAC in intact cells.
Starting Page	99
Ending Page	109
Page Count	11
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://jgp.rupress.org/content/jgp/130/1/99.full.pdf
PubMed reference number	17591988v1
Volume Number	130
Journal	The Journal of general physiology
Language	English
Access Restriction	Open
Subject Keyword	8-chloro-cyclic adenosine monophosphate ADCY10 gene Adenylate Cyclase Axoneme Cilia Fluorescence Resonance Energy Transfer Fluorescent Antibody Technique Tracer Western Blotting airway disease negative regulation of protein localization to ciliary membrane spindle assembly checkpoint
Content Type	Text
Resource Type	Article

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