title: Controlling fertilization and cAMP signaling in sperm by optogenetics.
abstract: Optogenetics is a powerful technique to control cellular activity by light. The light-gated Channelrhodopsin has been widely used to study and manipulate neuronal activity in vivo, whereas optogenetic control of second messengers in vivo has not been examined in depth. In this study, we present a transgenic mouse model expressing a photoactivated adenylyl cyclase (bPAC) in sperm. In transgenic sperm, bPAC mimics the action of the endogenous soluble adenylyl cyclase (SACY) that is required for motility and fertilization: light-stimulation rapidly elevates cAMP, accelerates the flagellar beat, and, thereby, changes swimming behavior of sperm. Furthermore, bPAC replaces endogenous adenylyl cyclase activity. In mutant sperm lacking the bicarbonate-stimulated SACY activity, bPAC restored motility after light-stimulation and, thereby, enabled sperm to fertilize oocytes in vitro. We show that optogenetic control of cAMP in vivo allows to non-invasively study cAMP signaling, to control behaviors of single cells, and to restore a fundamental biological process such as fertilization.
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Jansen
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Luis
authors.initials: L
authors.lastname: Alvarez
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Balbach
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Strünker
authors.affiliation: Institute of Biology, Experimental Biophysics, Humboldt University of Berlin, Berlin, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hegemann
authors.affiliation: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: U Benjamin
authors.initials: UB
authors.lastname: Kaupp
authors.affiliation: Minerva Research Group Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wachten
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP; D005298:Fertility / Q000528:radiation effects; D005306:Fertilization / Q000528:radiation effects; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D062308:Optogenetics / Q000379:methods*; D011479:Protamines / Q000235:genetics; D015398:Signal Transduction / Q000528:radiation effects; D012995:Solubility; D013081:Sperm Motility / Q000528:radiation effects; D013094:Spermatozoa / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D011479:Protamines; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium
keywords: cAMP; calcium; capacitation; cell biology; cyclic nucleotide signaling; mouse; optogenetics; sperm