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Ultrasensitive signal detection by a guanylyl cyclase chemoreceptor


Sperm navigate to the egg in a gradient of a chemoattractant for fertilization – a mechanism called chemotaxis. In sea urchin, the chemoattractant peptide binds to a chemoreceptor guanylyl cyclase (GC) on the sperm surface. Activation of the GC initiates a sequence of signaling events that eventually results in Ca2+ influx and a change in swimming direction. We studied the GC properties that allow sperm to track the chemoattractant with single-molecule precision on a millisecond time scale. A high density (9•103 GC molecules/µm2) and a subnanomolar ligand affinity provide a high ligand-capture efficacy. The sperm surface represents an almost perfect absorber. The peptide-induced GC activity is terminated by multiple dephosphorylation steps, which provide a means of precise lifetime control and, thereby, reduces “molecular noise”. Several experiments suggest that GC undergoes auto-dephosphorylation. Future experiments need to clarify, whether the GC entertains phosphatase and kinase activity, possibly in the kinase-homology domain (KHD). The turnover of cGMP synthesis of 72 cGMP molecules/sec or about 11 cGMP molecules/GC*/lifetime is sufficient to open a few cGMP-gated channels and to produce a unitary voltage response of about 2 mV. The receptor GC can bind the ligand over six orders of magnitude of concentrations. The shallow binding curve might reflect negative cooperativity among binding sites; alternatively receptor population might be composed of a mixture of receptors with a range of K1/2 values.

Figure 1
figure 1

Cellular signaling during chemotaxis in sea urchin sperm. The signaling events are initiated by binding of the ligand to the receptor GC. The rise of cGMP opens K+-selective cyclic nucleotide-gated channels (CNGK). The ensuing hyperpolarization activates a voltage-dependent Na+/H+ exchanger (NHE) and a pacemaker channel (HCN). The resulting alkalization by NHE and depolarization by HCN opens a sperm-specific Ca2+ channel (CatSper). Ca2+ is exported by a Na+/Ca2+-K+ exchanger (NCKX).

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Correspondence to U Benjamin Kaupp.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Kaupp, U.B. Ultrasensitive signal detection by a guanylyl cyclase chemoreceptor. BMC Pharmacol Toxicol 16 (Suppl 1), A20 (2015).

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