Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Signal., 10 July 2012
Vol. 5, Issue 232, p. ra48
[DOI: 10.1126/scisignal.2003110]

RESEARCH ARTICLES

Differential Regulation by Cyclic Nucleotides of the CNGA4 and CNGB1b Subunits in Olfactory Cyclic Nucleotide–Gated Channels

Vasilica Nache1, Thomas Zimmer1, Nisa Wongsamitkul1, Ralf Schmauder1, Jana Kusch1, Lisa Reinhardt1, Wolfgang Bönigk2, Reinhard Seifert2, Christoph Biskup1,3, Frank Schwede4, and Klaus Benndorf1*

1 Institute of Physiology II, University Hospital Jena, Friedrich-Schiller-University Jena, D-07740 Jena, Germany.
2 Center of Advanced European Studies and Research, Molecular Sensory Systems, Ludwig-Erhard-Allee 2, D-53175 Bonn, Germany.
3 Biomolecular Photonics Group, University Hospital Jena, Friedrich-Schiller-University Jena, D-07740 Jena, Germany.
4 BIOLOG Life Science Institute, Flughafendamm 9A, D-28199 Bremen, Germany.

Abstract: Olfactory cyclic nucleotide–gated (CNG) ion channels are essential contributors to signal transduction of olfactory sensory neurons. The activity of the channels is controlled by the cyclic nucleotides guanosine 3',5'-monophosphate (cGMP) and adenosine 3',5'-monophosphate (cAMP). The olfactory CNG channels are composed of two CNGA2 subunits, one CNGA4 and one CNGB1b subunit, each containing a cyclic nucleotide–binding domain. Using patch-clamp fluorometry, we measured ligand binding and channel activation simultaneously and showed that cGMP activated olfactory CNG channels not only by binding to the two CNGA2 subunits but also by binding to the CNGA4 subunit. In a channel in which the CNGA2 subunits were compromised for ligand binding, cGMP binding to CNGA4 was sufficient to partly activate the channel. In contrast, in heterotetrameric channels, the CNGB1b subunit did not bind cGMP, but channels with this subunit showed activation by cAMP. Thus, the modulatory subunits participate actively in translating ligand binding to activation of heterotetrameric olfactory CNG channels and enable the channels to differentiate between cyclic nucleotides.

* To whom correspondence should be addressed. E-mail: Klaus.Benndorf{at}mti.uni-jena.de

Citation: V. Nache, T. Zimmer, N. Wongsamitkul, R. Schmauder, J. Kusch, L. Reinhardt, W. Bönigk, R. Seifert, C. Biskup, F. Schwede, K. Benndorf, Differential Regulation by Cyclic Nucleotides of the CNGA4 and CNGB1b Subunits in Olfactory Cyclic Nucleotide–Gated Channels. Sci. Signal. 5, ra48 (2012).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A KcsA/MloK1 Chimeric Ion Channel Has Lipid-dependent Ligand-binding Energetics.
J. G. McCoy, R. Rusinova, D. M. Kim, J. Kowal, S. Banerjee, A. Jaramillo Cartagena, A. N. Thompson, L. Kolmakova-Partensky, H. Stahlberg, O. S. Andersen, et al. (2014)
J. Biol. Chem. 289, 9535-9546
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882