Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation.

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  • Additional Information
    • Source:
      Publisher: Wiley Blackwell Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE
    • Publication Information:
      Publication: 2014- : London : Wiley Blackwell
      Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-
    • Subject Terms:
      Chemotaxis* ; Proteomics* ; Signal Transduction*; Arbacia/*physiology; Animals ; Arbacia/ultrastructure ; Calcium/metabolism ; Cilia/physiology ; Cilia/ultrastructure ; Cyclic GMP/metabolism ; Electron Microscope Tomography ; Flagella/physiology ; Flagella/ultrastructure ; Guanylate Cyclase/metabolism ; Male ; Mass Spectrometry ; Spermatozoa/physiology ; Spermatozoa/ultrastructure
    • Abstract:
      Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca 2+ 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 Ca 2+ . 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.)
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    • Grant Information:
      SPP 1726 International Deutsche Forschungsgemeinschaft (DFG); R01 GM083122 United States GM NIGMS NIH HHS; RP170644 International Cancer Prevention and Research Institute of Texas (CPRIT); RR140082 International Cancer Prevention and Research Institute of Texas (CPRIT)
    • Contributed Indexing:
      Keywords: cilium; electron tomography; fertilization; quantitative mass spectrometry; signaling
    • Accession Number:
      EC 4.6.1.2 (Guanylate Cyclase)
      H2D2X058MU (Cyclic GMP)
      SY7Q814VUP (Calcium)
    • Publication Date:
      Date Created: 20191228 Date Completed: 20201028 Latest Revision: 20240725
    • Publication Date:
      20240726
    • Accession Number:
      PMC7024835
    • Accession Number:
      10.15252/embj.2019102723
    • Accession Number:
      31880004