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Bonigk, W.* ; Loogen, A.* ; Seifert, R.* ; Kashikar, N.* ; Klemm, C.* ; Krause, E.* ; Hagen, V.* ; Kremmer, E.* ; Strünker, T.* ; Kaupp, U.B.*

An atypical CNG channel activated by a single cGMP molecule controls sperm chemotaxis.

Sci. Signal. 2, ra68:ra68 (2010)
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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
Language english
Publication Year 2010
HGF-reported in Year 2010
ISSN (print) / ISBN 1945-0877
e-ISSN 1937-9145
Quellenangaben Volume: 2, Issue: 94, Pages: ra68 Article Number: ra68 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Reviewing status Peer reviewed
PSP Element(s) G-501700-003
PubMed ID 19861689
Scopus ID 74049087172
Erfassungsdatum 2010-10-14