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Open Access Green as soon as Postprint is submitted to ZB.
An atypical CNG channel activated by a single cGMP molecule controls sperm chemotaxis.
Sci. Signal. 2, ra68:ra68 (2010)
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 approximately 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 Ca(v) and Na(v) 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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Nucleotide-gated channels; Sea-urchin sperm; Ligand-binding; K+ Channel; Cyclic-nucleotides; Potassium channel; Structural basis; Genome; Efficacy; Chordate
ISSN (print) / ISBN
1945-0877
e-ISSN
1937-9145
Journal
Science Signaling
Quellenangaben
Volume: 2,
Issue: 94,
Pages: ra68
Article Number: ra68
Publisher
American Association for the Advancement of Science (AAAS)
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)