Volume 16 Supplement 1

Abstracts from the 7th International Conference on cGMP Generators, Effectors and Therapeutic Implications

Open Access

Ultrasensitive signal detection by a guanylyl cyclase chemoreceptor

BMC Pharmacology and Toxicology201516(Suppl 1):A20

DOI: 10.1186/2050-6511-16-S1-A20

Published: 2 September 2015

Background

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

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).

Authors’ Affiliations

(1)
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar)

Copyright

© Kaupp 2015

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 (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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