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Photoactivated adenylyl cyclase

January 01, 1970

Photoactivated adenylyl cyclase (PAC) is a protein consisting of an adenylyl cyclase enzyme domain directly linked to a BLUF (blue light receptor using FAD) type light sensor domain. When illuminated with blue light, the enzyme domain becomes active and converts ATP to cAMP, an important second messenger in many cells. In the unicellular flagellate Euglena gracilis, PACα and PACβ (euPACs) serve as a photoreceptor complex that senses light for photophobic responses and phototaxis.[2] Small but potent PACs were identified in the genome of the bacteria Beggiatoa (bPAC) and Oscillatoria acuminata (OaPAC).[3][1] While natural bPAC has some enzymatic activity in the absence of light, variants with no dark activity have been engineered (PACmn).[4]

Structure of the photoactivated adenylyl cyclase OaPAC forming a homodimer. FMN: flavin mononucleotide, the light-absorbing pigment. [1]

Use of PACs as optogenetic tools edit

As PACs consist of a light sensor and an enzyme in a single protein, they can be expressed in other species and cell types to manipulate cAMP levels with light. When bPAC is expressed in mouse sperm, blue light illumination speeds up the swimming of transgenic sperm cells and aids fertilization.[5] When expressed in neurons, illumination changes the branching pattern of growing axons.[6] PAC has been used in mice to clarify the function of neurons in the hypothalamus, which use cAMP signaling to control mating behavior.[7] Expression of PAC together with K+-specific cyclic-nucleotide-gated ion channels (CNGs) has been used to hyperpolarize neurons at very low light levels, which prevents them from firing action potentials.[8][9]

Rhodopsin guanylyl cyclases edit

Photoactivated guanylyl cyclases have been discovered in the aquatic fungi Blastocladiella emersonii[10][11] and Catenaria anguillulae.[12] Unlike PACs, these light-activated cyclases use retinal as their light sensor and are therefore rhodopsin guanylyl cyclases (RhGC). When expressed in Xenopus oocytes or mammalian neurons, RhGCs generate cGMP in response to green light.[12] Therefore, they are considered useful optogenetic tools to investigate cGMP signaling.[13]

References edit

  1. ^ a b Ohki, Mio; Sugiyama, Kanako; Kawai, Fumihiro; Tanaka, Hitomi; Nihei, Yuuki; Unzai, Satoru; Takebe, Masumi; Matsunaga, Shigeru; Adachi, Shin-ichi; Shibayama, Naoya; Zhou, Zhiwen (2016-05-31). "Structural insight into photoactivation of an adenylate cyclase from a photosynthetic cyanobacterium". Proceedings of the National Academy of Sciences. 113 (24): 6659–6664. Bibcode:2016PNAS..113.6659O. doi:10.1073/pnas.1517520113. ISSN 0027-8424. PMC 4914150. PMID 27247413.
  2. ^ Iseki, Mineo; Matsunaga, Shigeru; Murakami, Akio; Ohno, Kaoru; Shiga, Kiyoshi; Yoshida, Kazuichi; Sugai, Michizo; Takahashi, Tetsuo; Hori, Terumitsu; Watanabe, Masakatsu (2002-02-28). "A blue-light-activated adenylyl cyclase mediates photoavoidance in Euglena gracilis". Nature. 415 (6875): 1047–1051. Bibcode:2002Natur.415.1047I. doi:10.1038/4151047a. ISSN 1476-4687. PMID 11875575. S2CID 4420996.
  3. ^ Stierl, Manuela; Stumpf, Patrick; Udwari, Daniel; Gueta, Ronnie; Hagedorn, Rolf; Losi, Aba; Gärtner, Wolfgang; Petereit, Linda; Efetova, Marina; Schwarzel, Martin; Oertner, Thomas G. (2011-01-14). "Light Modulation of Cellular cAMP by a Small Bacterial Photoactivated Adenylyl Cyclase, bPAC, of the Soil Bacterium Beggiatoa". Journal of Biological Chemistry. 286 (2): 1181–1188. doi:10.1074/jbc.M110.185496. ISSN 0021-9258. PMC 3020725. PMID 21030594.
  4. ^ Yang, Shang; Constantin, Oana M.; Sachidanandan, Divya; Hofmann, Hannes; Kunz, Tobias C.; Kozjak-Pavlovic, Vera; Oertner, Thomas G.; Nagel, Georg; Kittel, Robert J.; Gee, Christine E.; Gao, Shiqiang (2021-10-18). "PACmn for improved optogenetic control of intracellular cAMP". BMC Biology. 19 (1): 227. doi:10.1186/s12915-021-01151-9. ISSN 1741-7007. PMC 8522238. PMID 34663304.
  5. ^ Jansen, Vera; Alvarez, Luis; Balbach, Melanie; Strünker, Timo; Hegemann, Peter; Kaupp, U Benjamin; Wachten, Dagmar (2015-01-20). "Controlling fertilization and cAMP signaling in sperm by optogenetics". eLife. 4: e05161. doi:10.7554/eLife.05161. ISSN 2050-084X. PMC 4298566. PMID 25601414.
  6. ^ Zhou, Zhiwen; Tanaka, Kenji F.; Matsunaga, Shigeru; Iseki, Mineo; Watanabe, Masakatsu; Matsuki, Norio; Ikegaya, Yuji; Koyama, Ryuta (2016-01-22). "Photoactivated adenylyl cyclase (PAC) reveals novel mechanisms underlying cAMP-dependent axonal morphogenesis". Scientific Reports. 6 (1): 19679. Bibcode:2016NatSR...519679Z. doi:10.1038/srep19679. ISSN 2045-2322. PMC 4726437. PMID 26795422.
  7. ^ Zhang, Stephen X.; Lutas, Andrew; Yang, Shang; Diaz, Adriana; Fluhr, Hugo; Nagel, Georg; Gao, Shiqiang; Andermann, Mark L. (2021-09-09). "Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling". Nature. 597 (7875): 245–249. Bibcode:2021Natur.597..245Z. doi:10.1038/s41586-021-03845-0. ISSN 0028-0836. PMC 8884112. PMID 34433964.
  8. ^ Beck, Sebastian; Yu-Strzelczyk, Jing; Pauls, Dennis; Constantin, Oana M.; Gee, Christine E.; Ehmann, Nadine; Kittel, Robert J.; Nagel, Georg; Gao, Shiqiang (2018-10-02). "Synthetic Light-Activated Ion Channels for Optogenetic Activation and Inhibition". Frontiers in Neuroscience. 12: 643. doi:10.3389/fnins.2018.00643. ISSN 1662-453X. PMC 6176052. PMID 30333716.
  9. ^ Bernal Sierra, Yinth Andrea; Rost, Benjamin R.; Pofahl, Martin; Fernandes, António Miguel; Kopton, Ramona A.; Moser, Sylvain; Holtkamp, Dominik; Masala, Nicola; Beed, Prateep; Tukker, John J.; Oldani, Silvia (2018). "Potassium channel-based optogenetic silencing". Nature Communications. 9 (1): 4611. Bibcode:2018NatCo...9.4611B. doi:10.1038/s41467-018-07038-8. ISSN 2041-1723. PMC 6218482. PMID 30397200.
  10. ^ Scheib, Ulrike; Stehfest, Katja; Gee, Christine E.; Körschen, Heinz G.; Fudim, Roman; Oertner, Thomas G.; Hegemann, Peter (2015-08-11). "The rhodopsin–guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling". Science Signaling. 8 (389): rs8. doi:10.1126/scisignal.aab0611. ISSN 1945-0877. PMID 26268609. S2CID 13140205.
  11. ^ Avelar, Gabriela M; Schumacher, Robert I; Zaini, Paulo A; Leonard, Guy; Richards, Thomas A; Gomes, Suely L (2014). "A Rhodopsin-Guanylyl Cyclase Gene Fusion Functions in Visual Perception in a Fungus". Current Biology. 24 (11): 1234–1240. doi:10.1016/j.cub.2014.04.009. PMC 4046227. PMID 24835457.
  12. ^ a b Scheib, Ulrike; Broser, Matthias; Constantin, Oana M.; Yang, Shang; Gao, Shiqiang; Mukherjee, Shatanik; Stehfest, Katja; Nagel, Georg; Gee, Christine E.; Hegemann, Peter (2018). "Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 Å structure of the adenylyl cyclase domain". Nature Communications. 9 (1): 2046. Bibcode:2018NatCo...9.2046S. doi:10.1038/s41467-018-04428-w. ISSN 2041-1723. PMC 5967339. PMID 29799525.
  13. ^ Rost, Benjamin R.; Schneider-Warme, Franziska; Schmitz, Dietmar; Hegemann, Peter (2017). "Optogenetic Tools for Subcellular Applications in Neuroscience". Neuron. 96 (3): 572–603. doi:10.1016/j.neuron.2017.09.047. PMID 29096074.

January 01, 1970
photoactivated, adenylyl, cyclase, protein, consisting, adenylyl, cyclase, enzyme, domain, directly, linked, bluf, blue, light, receptor, using, type, light, sensor, domain, when, illuminated, with, blue, light, enzyme, domain, becomes, active, converts, camp,. Photoactivated adenylyl cyclase PAC is a protein consisting of an adenylyl cyclase enzyme domain directly linked to a BLUF blue light receptor using FAD type light sensor domain When illuminated with blue light the enzyme domain becomes active and converts ATP to cAMP an important second messenger in many cells In the unicellular flagellate Euglena gracilis PACa and PACb euPACs serve as a photoreceptor complex that senses light for photophobic responses and phototaxis 2 Small but potent PACs were identified in the genome of the bacteria Beggiatoa bPAC and Oscillatoria acuminata OaPAC 3 1 While natural bPAC has some enzymatic activity in the absence of light variants with no dark activity have been engineered PACmn 4 Structure of the photoactivated adenylyl cyclase OaPAC forming a homodimer FMN flavin mononucleotide the light absorbing pigment 1 Use of PACs as optogenetic tools editAs PACs consist of a light sensor and an enzyme in a single protein they can be expressed in other species and cell types to manipulate cAMP levels with light When bPAC is expressed in mouse sperm blue light illumination speeds up the swimming of transgenic sperm cells and aids fertilization 5 When expressed in neurons illumination changes the branching pattern of growing axons 6 PAC has been used in mice to clarify the function of neurons in the hypothalamus which use cAMP signaling to control mating behavior 7 Expression of PAC together with K specific cyclic nucleotide gated ion channels CNGs has been used to hyperpolarize neurons at very low light levels which prevents them from firing action potentials 8 9 Rhodopsin guanylyl cyclases editPhotoactivated guanylyl cyclases have been discovered in the aquatic fungi Blastocladiella emersonii 10 11 and Catenaria anguillulae 12 Unlike PACs these light activated cyclases use retinal as their light sensor and are therefore rhodopsin guanylyl cyclases RhGC When expressed in Xenopus oocytes or mammalian neurons RhGCs generate cGMP in response to green light 12 Therefore they are considered useful optogenetic tools to investigate cGMP signaling 13 References edit a b Ohki Mio Sugiyama Kanako Kawai Fumihiro Tanaka Hitomi Nihei Yuuki Unzai Satoru Takebe Masumi Matsunaga Shigeru Adachi Shin ichi Shibayama Naoya Zhou Zhiwen 2016 05 31 Structural insight into photoactivation of an adenylate cyclase from a photosynthetic cyanobacterium Proceedings of the National Academy of Sciences 113 24 6659 6664 Bibcode 2016PNAS 113 6659O doi 10 1073 pnas 1517520113 ISSN 0027 8424 PMC 4914150 PMID 27247413 Iseki Mineo Matsunaga Shigeru Murakami Akio Ohno Kaoru Shiga Kiyoshi Yoshida Kazuichi Sugai Michizo Takahashi Tetsuo Hori Terumitsu Watanabe Masakatsu 2002 02 28 A blue light activated adenylyl cyclase mediates photoavoidance in Euglena gracilis Nature 415 6875 1047 1051 Bibcode 2002Natur 415 1047I doi 10 1038 4151047a ISSN 1476 4687 PMID 11875575 S2CID 4420996 Stierl Manuela Stumpf Patrick Udwari Daniel Gueta Ronnie Hagedorn Rolf Losi Aba Gartner Wolfgang Petereit Linda Efetova Marina Schwarzel Martin Oertner Thomas G 2011 01 14 Light Modulation of Cellular cAMP by a Small Bacterial Photoactivated Adenylyl Cyclase bPAC of the Soil Bacterium Beggiatoa Journal of Biological Chemistry 286 2 1181 1188 doi 10 1074 jbc M110 185496 ISSN 0021 9258 PMC 3020725 PMID 21030594 Yang Shang Constantin Oana M Sachidanandan Divya Hofmann Hannes Kunz Tobias C Kozjak Pavlovic Vera Oertner Thomas G Nagel Georg Kittel Robert J Gee Christine E Gao Shiqiang 2021 10 18 PACmn for improved optogenetic control of intracellular cAMP BMC Biology 19 1 227 doi 10 1186 s12915 021 01151 9 ISSN 1741 7007 PMC 8522238 PMID 34663304 Jansen Vera Alvarez Luis Balbach Melanie Strunker Timo Hegemann Peter Kaupp U Benjamin Wachten Dagmar 2015 01 20 Controlling fertilization and cAMP signaling in sperm by optogenetics eLife 4 e05161 doi 10 7554 eLife 05161 ISSN 2050 084X PMC 4298566 PMID 25601414 Zhou Zhiwen Tanaka Kenji F Matsunaga Shigeru Iseki Mineo Watanabe Masakatsu Matsuki Norio Ikegaya Yuji Koyama Ryuta 2016 01 22 Photoactivated adenylyl cyclase PAC reveals novel mechanisms underlying cAMP dependent axonal morphogenesis Scientific Reports 6 1 19679 Bibcode 2016NatSR 519679Z doi 10 1038 srep19679 ISSN 2045 2322 PMC 4726437 PMID 26795422 Zhang Stephen X Lutas Andrew Yang Shang Diaz Adriana Fluhr Hugo Nagel Georg Gao Shiqiang Andermann Mark L 2021 09 09 Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling Nature 597 7875 245 249 Bibcode 2021Natur 597 245Z doi 10 1038 s41586 021 03845 0 ISSN 0028 0836 PMC 8884112 PMID 34433964 Beck Sebastian Yu Strzelczyk Jing Pauls Dennis Constantin Oana M Gee Christine E Ehmann Nadine Kittel Robert J Nagel Georg Gao Shiqiang 2018 10 02 Synthetic Light Activated Ion Channels for Optogenetic Activation and Inhibition Frontiers in Neuroscience 12 643 doi 10 3389 fnins 2018 00643 ISSN 1662 453X PMC 6176052 PMID 30333716 Bernal Sierra Yinth Andrea Rost Benjamin R Pofahl Martin Fernandes Antonio Miguel Kopton Ramona A Moser Sylvain Holtkamp Dominik Masala Nicola Beed Prateep Tukker John J Oldani Silvia 2018 Potassium channel based optogenetic silencing Nature Communications 9 1 4611 Bibcode 2018NatCo 9 4611B doi 10 1038 s41467 018 07038 8 ISSN 2041 1723 PMC 6218482 PMID 30397200 Scheib Ulrike Stehfest Katja Gee Christine E Korschen Heinz G Fudim Roman Oertner Thomas G Hegemann Peter 2015 08 11 The rhodopsin guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling Science Signaling 8 389 rs8 doi 10 1126 scisignal aab0611 ISSN 1945 0877 PMID 26268609 S2CID 13140205 Avelar Gabriela M Schumacher Robert I Zaini Paulo A Leonard Guy Richards Thomas A Gomes Suely L 2014 A Rhodopsin Guanylyl Cyclase Gene Fusion Functions in Visual Perception in a Fungus Current Biology 24 11 1234 1240 doi 10 1016 j cub 2014 04 009 PMC 4046227 PMID 24835457 a b Scheib Ulrike Broser Matthias Constantin Oana M Yang Shang Gao Shiqiang Mukherjee Shatanik Stehfest Katja Nagel Georg Gee Christine E Hegemann Peter 2018 Rhodopsin cyclases for photocontrol of cGMP cAMP and 2 3 A structure of the adenylyl cyclase domain Nature Communications 9 1 2046 Bibcode 2018NatCo 9 2046S doi 10 1038 s41467 018 04428 w ISSN 2041 1723 PMC 5967339 PMID 29799525 Rost Benjamin R Schneider Warme Franziska Schmitz Dietmar Hegemann Peter 2017 Optogenetic Tools for Subcellular Applications in Neuroscience Neuron 96 3 572 603 doi 10 1016 j neuron 2017 09 047 PMID 29096074 Retrieved from https en wikipedia org w index php title Photoactivated adenylyl cyclase amp oldid 1187422473, wikipedia, wiki, book, books, library,

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