{"date_created":"2019-03-20T14:05:06Z","extern":"1","year":"2013","citation":{"short":"A. Couto, S. Oda, V.O. Nikolaev, Z. Soltesz, M. de Bono, Proceedings of the National Academy of Sciences 110 (2013) E3301–E3310.","apa":"Couto, A., Oda, S., Nikolaev, V. O., Soltesz, Z., &#38; de Bono, M. (2013). In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor. <i>Proceedings of the National Academy of Sciences</i>. Proceedings of the National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1217428110\">https://doi.org/10.1073/pnas.1217428110</a>","chicago":"Couto, A., S. Oda, V. O. Nikolaev, Z. Soltesz, and Mario de Bono. “In Vivo Genetic Dissection of O2-Evoked CGMP Dynamics in a Caenorhabditis Elegans Gas Sensor.” <i>Proceedings of the National Academy of Sciences</i>. Proceedings of the National Academy of Sciences, 2013. <a href=\"https://doi.org/10.1073/pnas.1217428110\">https://doi.org/10.1073/pnas.1217428110</a>.","ista":"Couto A, Oda S, Nikolaev VO, Soltesz Z, de Bono M. 2013. In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor. Proceedings of the National Academy of Sciences. 110(35), E3301–E3310.","mla":"Couto, A., et al. “In Vivo Genetic Dissection of O2-Evoked CGMP Dynamics in a Caenorhabditis Elegans Gas Sensor.” <i>Proceedings of the National Academy of Sciences</i>, vol. 110, no. 35, Proceedings of the National Academy of Sciences, 2013, pp. E3301–10, doi:<a href=\"https://doi.org/10.1073/pnas.1217428110\">10.1073/pnas.1217428110</a>.","ieee":"A. Couto, S. Oda, V. O. Nikolaev, Z. Soltesz, and M. de Bono, “In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor,” <i>Proceedings of the National Academy of Sciences</i>, vol. 110, no. 35. Proceedings of the National Academy of Sciences, pp. E3301–E3310, 2013.","ama":"Couto A, Oda S, Nikolaev VO, Soltesz Z, de Bono M. In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor. <i>Proceedings of the National Academy of Sciences</i>. 2013;110(35):E3301-E3310. doi:<a href=\"https://doi.org/10.1073/pnas.1217428110\">10.1073/pnas.1217428110</a>"},"type":"journal_article","author":[{"first_name":"A.","full_name":"Couto, A.","last_name":"Couto"},{"full_name":"Oda, S.","last_name":"Oda","first_name":"S."},{"first_name":"V. O.","full_name":"Nikolaev, V. O.","last_name":"Nikolaev"},{"last_name":"Soltesz","full_name":"Soltesz, Z.","first_name":"Z."},{"first_name":"Mario","orcid":"0000-0001-8347-0443","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","full_name":"de Bono, Mario","last_name":"de Bono"}],"status":"public","has_accepted_license":"1","abstract":[{"text":"cGMP signaling is widespread in the nervous system. However, it has proved difficult to visualize and genetically probe endogenously evoked cGMP dynamics in neurons in vivo. Here, we combine cGMP and Ca2+ biosensors to image and dissect a cGMP signaling network in a Caenorhabditis elegans oxygen-sensing neuron. We show that a rise in O2 can evoke a tonic increase in cGMP that requires an atypical O2-binding soluble guanylate cyclase and that is sustained until oxygen levels fall. Increased cGMP leads to a sustained Ca2+ response in the neuron that depends on cGMP-gated ion channels. Elevated levels of cGMP and Ca2+ stimulate competing negative feedback loops that shape cGMP dynamics. Ca2+-dependent negative feedback loops, including activation of phosphodiesterase-1 (PDE-1), dampen the rise of cGMP. A different negative feedback loop, mediated by phosphodiesterase-2 (PDE-2) and stimulated by cGMP-dependent kinase (PKG), unexpectedly promotes cGMP accumulation following a rise in O2, apparently by keeping in check gating of cGMP channels and limiting activation of Ca2+-dependent negative feedback loops. Simultaneous imaging of Ca2+ and cGMP suggests that cGMP levels can rise close to cGMP channels while falling elsewhere. O2-evoked cGMP and Ca2+ responses are highly reproducible when the same neuron in an individual animal is stimulated repeatedly, suggesting that cGMP transduction has high intrinsic reliability. However, responses vary substantially across individuals, despite animals being genetically identical and similarly reared. This variability may reflect stochastic differences in expression of cGMP signaling components. Our work provides in vivo insights into the architecture of neuronal cGMP signaling.","lang":"eng"}],"date_published":"2013-08-27T00:00:00Z","page":"E3301-E3310","publication_status":"published","month":"08","date_updated":"2021-01-12T08:06:16Z","ddc":["570"],"file":[{"content_type":"application/pdf","file_size":2198763,"access_level":"open_access","date_updated":"2020-07-14T12:47:20Z","checksum":"3ee28a694f74a49f0d098970ae391a91","relation":"main_file","date_created":"2019-03-20T14:07:53Z","creator":"kschuh","file_id":"6134","file_name":"2013_PNAS_Couto.pdf"}],"publisher":"Proceedings of the National Academy of Sciences","volume":110,"oa_version":"Published Version","day":"27","intvolume":"       110","file_date_updated":"2020-07-14T12:47:20Z","_id":"6133","pmid":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0027-8424","1091-6490"]},"oa":1,"issue":"35","title":"In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor","quality_controlled":"1","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["23940325"]},"doi":"10.1073/pnas.1217428110","publication":"Proceedings of the National Academy of Sciences"}