Ultrasensitive signal detection by a guanylyl cyclase chemoreceptor
BMC Pharmacology and Toxicology volume 16, Article number: A20 (2015)
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.
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Kaupp, U.B. Ultrasensitive signal detection by a guanylyl cyclase chemoreceptor. BMC Pharmacol Toxicol 16 (Suppl 1), A20 (2015). https://doi.org/10.1186/2050-6511-16-S1-A20