Cyclic Nucleotide-Specific Optogenetics Highlights Compartmentalization of the Sperm Flagellum into cAMP Microdomains

Cells. 2019 Jun 27;8(7):648. doi: 10.3390/cells8070648.

Abstract

Inside the female genital tract, mammalian sperm undergo a maturation process called capacitation, which primes the sperm to navigate across the oviduct and fertilize the egg. Sperm capacitation and motility are controlled by 3',5'-cyclic adenosine monophosphate (cAMP). Here, we show that optogenetics, the control of cellular signaling by genetically encoded light-activated proteins, allows to manipulate cAMP dynamics in sperm flagella and, thereby, sperm capacitation and motility by light. To this end, we used sperm that express the light-activated phosphodiesterase LAPD or the photo-activated adenylate cyclase bPAC. The control of cAMP by LAPD or bPAC combined with pharmacological interventions provides spatiotemporal precision and allows to probe the physiological function of cAMP compartmentalization in mammalian sperm.

Keywords: beat pattern; cAMP; cilia; flagella; motility; navigation; optogenetics; sperm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP / metabolism*
  • Enzyme Assays
  • Light
  • Male
  • Mice
  • Mice, Transgenic
  • Optogenetics / methods*
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / metabolism
  • Phosphoric Diester Hydrolases / radiation effects
  • Spatio-Temporal Analysis
  • Sperm Capacitation / physiology*
  • Sperm Motility / physiology*
  • Sperm Tail / metabolism*

Substances

  • Cyclic AMP
  • Phosphoric Diester Hydrolases