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Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation

ABSTRACT: Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca2+rise that controls motility. The mechanisms underlying such ultra-sensitivity are ill-defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin Arbacia punctulata. Proteins are up to 1,000-fold more abundant than the free cellular messengers cAMP, cGMP, H+, and Ca2+. Opto-chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP-gated channel that serves as a perfect chemo-electrical transducer. cGMP is rapidly hydrolyzed, possibly via 'substrate channeling' from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate-detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification - few enzyme molecules process many messenger molecules - does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.

SUBMITTER: Dr. U., Benjamin Kaupp

PROVIDER: S-SCDT-EMBOJ-2019-102723P | biostudies-other |

REPOSITORIES: biostudies-other

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