Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation

Christian Trötschel, Hussein Hamzeh, Luis Alvarez, René Pascal, Fedir Lavryk, Wolfgang Bönigk, Heinz G. Körschen, Astrid Müller, Ansgar Poetsch, Andreas Rennhack, Long Gui, Daniela Nicastro, Timo Strünker, Reinhard Seifert, U. Benjamin Kaupp

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Article numbere102723
JournalEMBO Journal
Issue number4
StatePublished - Feb 17 2020


  • cilium
  • electron tomography
  • fertilization
  • quantitative mass spectrometry
  • signaling

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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