Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation

• Christian Trötschel ^[2] ; Hussein Hamzeh ^[3] ; Luis Alvarez ^[4] ; René Pascal ^[4] ; Fedir Lavryk ^[4] ; Wolfgang Bönigk ^[4] ; Heinz G Körschen ^[4] ; Astrid Müller ^[4] ; Ansgar Poetsch ^[5] ; Andreas Rennhack ^[4] ; Long Gui ^[1] ; Daniela Nicastro ^[1] ; Timo Strünker ^[6] ; Reinhard Seifert ^[3] ; U Benjamin Kaupp ^[7]
  1. [1] University of Texas Southwestern Medical Center

     University of Texas Southwestern Medical Center

     Estados Unidos

     
  2. [2] 1 Fakultät für Biologie und Biotechnologie Ruhr‐Universität Bochum Bochum Germany
  3. [3] 2 Center of Advanced European Studies and Research (caesar), Molecular Sensory Systems Bonn Germany; 3 Marine Biological Laboratory Woods Hole MA USA
  4. [4] 2 Center of Advanced European Studies and Research (caesar), Molecular Sensory Systems Bonn Germany
  5. [5] 1 Fakultät für Biologie und Biotechnologie Ruhr‐Universität Bochum Bochum Germany; 7Present address: Center for Marine and Molecular Biotechnology QNLM Qindao China; 8Present address: College of Marine Life Sciences Ocean University of China Qingdao China
  6. [6] 2 Center of Advanced European Studies and Research (caesar), Molecular Sensory Systems Bonn Germany; 3 Marine Biological Laboratory Woods Hole MA USA; 5 Center of Reproductive Medicine and Andrology University Hospital Münster Münster Germany
  7. [7] 2 Center of Advanced European Studies and Research (caesar), Molecular Sensory Systems Bonn Germany; 3 Marine Biological Laboratory Woods Hole MA USA; 6 Life& Medical Sciences Institute (LIMES) University of Bonn Bonn Germany

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 39, Nº. 4, 2020
• Idioma: inglés
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  • 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.