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.

中文翻译：

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绝对蛋白质组定量揭示了精子鞭毛化学感应的设计原理。


纤毛充当细胞天线，将感觉信息转化为生理反应。在精子鞭毛中，单个化学引诱剂分子可以引发控制精子活力的 Ca2+ 升高。这种超敏感性背后的机制尚不清楚。在这里，我们通过质谱法测定了海胆 Arbacia punctulata 精子鞭毛中 19 种化学感应信号蛋白的拷贝数。蛋白质的含量比游离细胞信使 cAMP、cGMP、H+ 和 Ca2+ 丰富达 1,000 倍。光化学技术表明，高蛋白质浓度会在动力学上划分鞭毛：在几毫秒内，cGMP 从受体鸟苷酸环化酶传递到 cGMP 门控通道，该通道充当完美的化学电转换器。 cGMP 可能通过“底物通道”从通道快速水解至磷酸二酯酶 PDE5。通道/PDE5 串联编码 cGMP 周转率而不是浓度。速率检测机制允许在宽动态范围内连续刺激采样。教科书上的信号放大概念——很少的酶分子处理很多信使分子——并不适用于精子鞭毛。相反，高蛋白质浓度可以确定信使的检测。类似的机制可能发生在其他小室中，如初级纤毛或树突棘。