Kantonsspital St.Gallen

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

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 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.
citation 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.
type journal paper/review (English)
date of publishing 27-10-2009
journal title Sci Signal (2/94)
ISSN electronic 1937-9145
pages ra68
PubMed 19861689
DOI 10.1126/scisignal.2000516