Signal Transduction

Single-Molecule Sensitivity

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Science  06 Nov 2009:
Vol. 326, Issue 5954, pp. 773
DOI: 10.1126/science.326_773c

The external fertilization of sea urchin eggs relies on an extreme sensitivity of the sperm to chemoattractant molecules that guide the sperm toward the egg. In fact, Arbacia punctulata sperm can sense a single molecule of chemoattractant. Bönigk et al. show that such sensitivity is not limited to the receptor-type guanylyl cyclase that is located on the sperm cell membrane and detects the chemoattractant. This enzyme makes the second messenger cyclic guanosine monophosphate (cGMP), and the cGMP produced is detected with single-molecule sensitivity by K+-selective cyclic nucleotide-gated (CNGK) channels. Binding to only one of the four cGMPbinding sites on the tetrameric channel was sufficient to open the channel. The authors also deployed a caged form of cGMP, in which photolysis breaks the cage and releases cGMP with a concomitant fluorescence signal. This reagent allowed them to estimate that less than 50 molecules of cGMP were formed in response to a single molecule of chemoattractant. Only a small fraction of these are likely to diffuse and bind to a channel because of competing binding sites and degradation pathways in the cell. The authors propose that other high-affinity receptors for neurotransmitters and hormones may also display single-molecule sensitivity.

Sci. Signal. 2, ra68 (2009).

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