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Vera Jansen1,2author-20646, Luis Alvarez1author-20647, Melanie Balbach1author-20648, Timo Strünker1author-7349, Peter Hegemann3author-20650, U Benjamin Kaupp1,*author-3783 and Dagmar Wachten2,*author-192051Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany2Minerva Research Group Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany3Institute of Biology, Experimental Biophysics, Humboldt University of Berlin, Berlin, Germany↵*For correspondence: U.B.Kaupp{at}caesar.de (UBK);↵dagmar.wachten{at}caesar.de (DW)David E Clapham, Reviewing editorHoward Hughes Medical Institute, Boston Children's Hospital, United States↵VJ, Conception and design, Acquisition of data, Analysis and interpretation of data, Drafting or revising the article↵LA, Conception and design, Analysis and interpretation of data, Contributed unpublished essential data or reagents↵MB, Acquisition of data, Analysis and interpretation of data↵TS, Conception and design, Analysis and interpretation of data, Drafting or revising the article↵DW, Conception and design, Analysis and interpretation of data, Drafting or revising the article↵PH, Drafting or revising the article, Contributed unpublished essential data or reagents↵UBK, Conception and design, Drafting or revising the articleAbstractOptogenetics is a powerful technique to control cellular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.DOI: http://dx.doi.org/10.7554/eLife.05161.001Author keywordscyclic nucleotide signalingspermcapacitationcAMPcalciumoptogeneticsResearch organismmouseFootnotes↵The authors declare that no competing interests exist.Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the LANUV (Landesamt für Natur, Umwelt und Verbraucherschutz). Reference number: 84-02.04.2012.A192.Received October 14, 2014.Accepted December 22, 2014.© 2014, Jansen et alThis article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
