An atypical CNG channel activated by a single cGMP molecule controls sperm chemotaxis
Wolfgang Bönigk, Astrid Loogen, Reinhard Seifert, Nachiket Kashikar, Clementine Klemm, Eberhard Krause, Volker Hagen, Elisabeth Kremmer, Timo Strünker & U Benjamin Kaupp
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abstract
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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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citation
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Bönigk 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 2009; 2:ra68.
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type
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journal paper/review (English)
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date of publishing
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27-10-2009
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journal title
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Sci Signal (2/94)
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ISSN electronic
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1937-9145
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pages
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ra68
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PubMed
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19861689
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DOI
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10.1126/scisignal.2000516
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