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Sci. Signal., 27 October 2009
Vol. 2, Issue 94, p. ra68
[DOI: 10.1126/scisignal.2000516]

RESEARCH ARTICLES

An Atypical CNG Channel Activated by a Single cGMP Molecule Controls Sperm Chemotaxis

Wolfgang Bönigk1,2*, Astrid Loogen1*, Reinhard Seifert1*, Nachiket Kashikar1,3, Clementine Klemm4, Eberhard Krause4, Volker Hagen4, Elisabeth Kremmer5, Timo Strünker1,3, and U. Benjamin Kaupp1,3{dagger}

1 Center of Advanced European Studies and Research, Abteilung Molekulare Neurosensorik, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany.
2 Institut für Strukturbiologie und Biophysik, ISB-1, Forschungszentrum Jülich, 52425 Jülich, Germany.
3 Marine Biological Laboratory, Woods Hole, MA 02543, USA.
4 Leibniz-Institut für Molekulare Pharmakologie, Robert-Rössle-Straße 10, 13125 Berlin, Germany.
5 Helmholtz-Zentrum München, Institut für Molekulare Immunologie, Marchioninistraße 52, 81377 Munich, Germany.

* These authors contributed equally to this work.

Abstract: Sperm of the sea urchin Arbacia punctulata can respond to a single molecule of chemoattractant released by an egg. The mechanism underlying this extreme sensitivity is unknown. Crucial signaling events in the response of A. punctulata sperm to chemoattractant include the rapid synthesis of the intracellular messenger guanosine 3',5'-monophosphate (cGMP) and the ensuing membrane hyperpolarization that results from the opening of potassium–selective cyclic nucleotide–gated (CNGK) channels. Here, we use calibrated photolysis of caged cGMP to show that ~45 cGMP molecules are generated during the response to a single molecule of chemoattractant. The CNGK channel can respond to such small cGMP changes because it is exquisitely sensitive to cGMP and activated in a noncooperative fashion. Like voltage-activated Cav and Nav channels, the CNGK polypeptide consists of four homologous repeat sequences. Disabling each of the four cyclic nucleotide–binding sites through mutagenesis revealed that binding of a single cGMP molecule to repeat 3 is necessary and sufficient to activate the CNGK channel. Thus, CNGK has developed a mechanism of activation that is different from the activation of other CNG channels, which requires the cooperative binding of several ligands and operates in the micromolar rather than the nanomolar range.

{dagger} To whom correspondence should be addressed. E-mail: u.b.kaupp{at}caesar.de

Citation: W. Bönigk, A. Loogen, R. Seifert, N. Kashikar, C. Klemm, E. Krause, V. Hagen, E. Kremmer, T. Strünker, U. B. Kaupp, An Atypical CNG Channel Activated by a Single cGMP Molecule Controls Sperm Chemotaxis. Sci. Signal. 2, ra68 (2009).

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