Controlling fertilization and cAMP signaling in sperm by optogenetics
Vera Jansen,
Luis Alvarez,
Melanie Balbach,
Timo Strünker,
Peter Hegemann,
U Benjamin Kaupp,
Dagmar Wachten
Affiliations
Vera Jansen
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany; Minerva Research Group Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany
Luis Alvarez
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany
Melanie Balbach
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany
Timo Strünker
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany
Peter Hegemann
Institute of Biology, Experimental Biophysics, Humboldt University of Berlin, Berlin, Germany
U Benjamin Kaupp
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany
Dagmar Wachten
Minerva Research Group Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany
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.
