Faculty Opinions recommendation of Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation.
Year: 2020
Type: peer-review
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.© 2019 The Authors. Published under the terms of the CC BY NC ND 4.0 license. PMID: 31880004 Funding information This work was supported by: Cancer Prevention and Research Institute of Texas (CPRIT), Grant ID: RR140082 Cancer Prevention and Research Institute of Texas (CPRIT), Grant ID: RP170644 Deutsche Forschungsgemeinschaft (DFG), Grant ID: Cluster of Excellence 1023 NIGMS NIH HHS, United States Grant ID: R01 GM083122 Deutsche Forschungsgemeinschaft (DFG), Grant ID: SPP 1726
Authors: Karl Lechtreck, Jin Dai
Institution: University of Georgia
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4246464939