Article
Biochemistry & Molecular Biology
Hang Lam Li, Simei Go, Jung-Chin Chang, Arthur Verhoeven, Ronald Oude Elferink
Summary: This review highlights the distinct characteristics and crucial role of soluble adenylyl cyclase (sAC) in cellular processes, as well as recent significant advancements in the field of sAC research.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Biology
Tom Rossetti, Stephanie Jackvony, Jochen Buck, Lonny R. Levin
Summary: Soluble adenylyl cyclase (sAC) is a bicarbonate-regulated enzyme that acts as a sensor for HCO3-/CO2/pH, regulating diverse physiological functions.
Article
Biochemistry & Molecular Biology
Thi Mong Diep Nguyen, Laura Filliatreau, Daniele Klett, Nong Van Hai, Nguyen Thuy Duong, Yves Combarnous
Summary: The research reveals that ADCY10 is located in the cytoplasm and responds to four different inhibitors. These inhibitors can reduce cAMP accumulation in MTLC-1 cells and various Leydig cells, emphasizing the importance of ADCY10 in response to the hormone LH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Dermatology
Jaewon You, Michael D. Reilly, Mahmoud Eljalby, Rohan Bareja, Maftuna Yusupova, Nikki S. Vyas, Jakyung Bang, Wanhong Ding, Garrett Desman, Lloyd S. Miller, Olivier Elemento, Richard D. Granstein, Jonathan H. Zippin
Summary: This study demonstrates the importance of soluble adenylate cyclase (sAC) in psoriasis pathogenesis and identifies it as a potential therapeutic target. The absence of Adcy10 gene significantly reduces the symptoms of psoriasiform dermatitis in mice and inhibits the differentiation and gene expression of Th17 cells. Moreover, topical application of sAC inhibitors shows promise in reducing psoriasiform dermatitis and IL17 gene expression in the skin, suggesting their potential as topical therapeutics for Th17-mediated skin diseases.
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Kelsey F. Speer, Luella Allen-Waller, Dana R. Novikov, Katie L. Barott
Summary: The study identified a pH-sAC-cAMP signaling pathway in coral sperm that regulates sperm motility, and suggested its potential presence in many marine invertebrate taxa. This discovery highlights the ancient origin of this signaling pathway in sperm physiology and emphasizes the importance of understanding pH-dependent signaling in the reproductive success of marine animals under changing environmental conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Xuefeng Zhang, Alejandro Pizzoni, Kyoungja Hong, Nyla Naim, Chao Qi, Volodymyr Korkhov, Daniel L. Altschuler
Summary: CAP1 is a highly conserved protein involved in regulating cAMP dynamics in mammalian cells by binding and activating adenylyl cyclase, modulating cAMP levels in a Rap1-dependent manner, and affecting cAMP-dependent proliferation. The interaction between CAP1, cyclase, and Rap1 forms a regulatory unit that may be involved in establishing cAMP microdomains and localized signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Emil Jakobsen, Jens V. Andersen, Sofie K. Christensen, Olga Siamka, Martin R. Larsen, Helle S. Waagepetersen, Blanca I. Aldana, Lasse K. Bak
Summary: Pharmacologically induced inhibition of sAC activity lowers mitochondrial respiration, induces phosphorylation of AMP-activated protein kinase (AMPK), and decreases glycogen stores in cultured primary murine astrocytes. Mitochondrial sAC emerges as a key regulator of astrocyte bioenergetics, despite challenges in investigating the roles of cytosolic versus mitochondrial sAC in astrocytes using current pharmacological tools.
Article
Pharmacology & Pharmacy
Ellis Nelissen, Melissa Schepers, Laura Ponsaerts, Sebastien Foulquier, Annelies Bronckaers, Tim Vanmierlo, Peter Sandner, Jos Prickaerts
Summary: Vascular cognitive impairment (VCI) is a neurodegenerative disorder characterized by a vascular component, involving decreased cerebral blood flow, white matter lesions, endothelial dysfunction, and blood-brain barrier impairments. Oxidative stress and inflammation are major underlying mechanisms. Modulation of soluble guanylate cyclase (sGC) activity can improve vascular and neural function, and has shown efficacy in cardiovascular diseases.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Physiology
Katrina F. Ostrom, Justin E. LaVigne, Tarsis F. Brust, Roland Seifert, Carmen W. Dessauer, Val J. Watts, Rennolds S. Ostrom
Summary: Adenylyl cyclases (ACs) catalyze the conversion of ATP to cAMP, serving as major effectors of G protein-coupled receptors (GPCRs) with varying expression patterns across tissues. Understanding the potential roles of each isoform holds promise for uncovering new therapeutic approaches.
PHYSIOLOGICAL REVIEWS
(2022)
Article
Cell Biology
Mina Hwang, Hyo-Sup Kim, Sang-Man Jin, Kyoo-Yeon Hur, Jae-Hyeon Kim, Moon-Kyu Lee
Summary: Thiazolidinediones are synthetic PPAR gamma ligands that can enhance insulin sensitivity and potentially increase insulin secretion from pancreatic beta-cells, but the functional role and mechanism of action in beta-cells have not been thoroughly investigated.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biology
Shang Yang, Oana M. Constantin, Divya Sachidanandan, Hannes Hofmann, Tobias C. Kunz, Vera Kozjak-Pavlovic, Thomas G. Oertner, Georg Nagel, Robert J. Kittel, Christine E. Gee, Shiqiang Gao
Summary: The study engineered a membrane-anchored photoactivatable adenylyl cyclase that rapidly increases cAMP levels in response to light without accumulating cAMP in the dark. This optogenetic tool, PACmn, allows precise and transient stimulation of cAMP signaling pathways in diverse cell types, making it valuable for research in cell-autonomous signaling mechanisms.
Article
Multidisciplinary Sciences
Sarah Baudet, Yvrick Zagar, Fiona Roche, Claudia Gomez-Bravo, Sandrine Couvet, Johann Becret, Morgane Belle, Juliette Vougny, Sinthuya Uthayasuthan, Oriol Ros, Xavier Nicol
Summary: The study demonstrates that different axon guidance cues induce distinct intracellular signals, including cAMP, cGMP, and Ca2+, confined to separate cellular nanodomains. It challenges the traditional view that axon repellents and attractants share the same set of cellular messenger signals by showing that two repellent cues, ephrin-A5 and Slit1, activate spatially segregated signals. These findings reveal the importance of subcellular-specific second messenger crosstalk in controlling axonal morphology changes and pathfinding decisions.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jun Xu, Nobuo Koizumi, Yusuke V. Morimoto, Ryo Ozuru, Toshiyuki Masuzawa, Shuichi Nakamura
Summary: Nucleotide second messengers play crucial roles in signal transduction in various organisms. A study has found that the swimming motility of the soil bacterium Leptospira kobayashii can be rapidly modulated by light stimulation. Through analysis of a loss-of-photoresponsivity mutant, a novel sensory gene was identified, and the light-dependent synthesis of cyclic adenosine monophosphate (cAMP) was elucidated. These findings reveal a new role for cAMP in controlling the flagella-dependent motility of Leptospira and highlight the global distribution of the newly discovered photoactivated cyclase among diverse microbial species.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Ming Zhang, Hongbing Wang
Summary: The type 1 and 8 adenylyl cyclase (ADCY1 and ADCY8) are responsible for Ca2+-stimulated cyclic AMP (cAMP) production and play a role in activity-dependent synaptic modification. This study found that Adcy8(-/-) mice showed normal long-term potentiation (LTP), while Adcy1(-/-) mice showed deficits in LTP depending on the induction protocol. ADCY1 was found to be necessary for long-term depression (LTD), whereas ADCY8 was not. Both Adcy1(-/-) and Adcy8(-/-) mice showed defects in synaptic depotentiation, with Adcy8(-/-) mice's deficits depending on the induction protocol. ADCY1 was required for both initial and reversal memory formation, while ADCY8 was only necessary for reversal memory formation. These findings demonstrate that ADCY1 and ADCY8 have distinct roles in regulating synaptic and cognitive flexibility through bidirectional modulation of synaptic function.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Review
Cell Biology
Muhammad Aslam, Yury Ladilov
Summary: AMPK plays a crucial role in cellular and systemic energy homeostasis. There is a link between cAMP and AMPK signaling. In addition to its physiological role, the cAMP/AMPK axis also plays a significant role in pathologies such as inflammation, ischemia, diabetes, obesity, and aging.
Review
Physiology
Lonny R. Levin, Jochen Buck
ANNUAL REVIEW OF PHYSIOLOGY, VOL 77
(2015)
Article
Immunology
Richard L. Watson, Jochen Buck, Lonny R. Levin, Ryan C. Winger, Jing Wang, Hisashi Arase, William A. Muller
JOURNAL OF EXPERIMENTAL MEDICINE
(2015)
Article
Biochemistry & Molecular Biology
Silke Kleinboelting, Lavoisier Ramos-Espiritu, Hannes Buck, Laureen Colis, Joop van den Heuvel, J. Fraser Glickman, Lonny R. Levin, Jochen Buck, Clemens Steegborn
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Physiology
Nawreen Rahman, Lavoisier Ramos-Espiritu, Teresa A. Milner, Jochen Buck, Lonny R. Levin
JOURNAL OF GENERAL PHYSIOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Lavoisier Ramos-Espiritu, Silke Kleinboelting, Felipe A. Navarrete, Antonio Alvau, Pablo E. Visconti, Federica Valsecchi, Anatoly Starkov, Giovanni Manfredi, Hannes Buck, Carolina Adura, Jonathan H. Zippin, Joop van den Heuvel, J. Fraser Glickman, Clemens Steegborn, Lonny R. Levin, Jochen Buck
NATURE CHEMICAL BIOLOGY
(2016)
Article
Oncology
Lavoisier Ramos-Espiritu, Ana Diaz, Charlee Nardin, Anthony J. Saviola, Fiona Shaw, Tamar Plitt, Xia Yang, Jedd Wolchok, Edyta C. Pirog, Garrett Desman, Andrea Sboner, Tuo Zhang, Jenny Xiang, Taha Merghoub, Lonny R. Levin, Jochen Buck, Jonathan H. Zippin
Article
Neurosciences
Jennifer Martinez, Alexander M. Stessin, Aline Campana, Jianwei Hou, Elena Nikulina, Jochen Buck, Lonny R. Levin, Marie T. Filbin
JOURNAL OF NEUROSCIENCE
(2014)
Article
Multidisciplinary Sciences
Silke Kleinboelting, Ana Diaz, Sebastien Moniot, Joop van den Heuvel, Michael Weyand, Lonny R. Levin, Jochen Buck, Clemens Steegborn
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2014)
Article
Multidisciplinary Sciences
Felipe A. Navarrete, Antonio Alvau, Hoi Chang Lee, Lonny R. Levin, Jochen Buck, Patricia Martin-De Leon, Celia M. Santi, Dario Krapf, Jesse Mager, Rafael A. Fissore, Ana M. Salicioni, Alberto Darszon, Pablo E. Visconti
SCIENTIFIC REPORTS
(2016)
Article
Biochemistry & Molecular Biology
Dalee Zhou, Koji Ota, Charlee Nardin, Michelle Feldman, Adam Widman, Olivia Wind, Amanda Simon, Michael Reilly, Lonny R. Levin, Jochen Buck, Kazumasa Wakamatsu, Shosuke Ito, Jonathan H. Zippin
Article
Chemistry, Medicinal
Michael Miller, Thomas Rossetti, Jacob Ferreira, Lubna Ghanem, Melanie Balbach, Navpreet Kaur, Lonny R. Levin, Jochen Buck, Maria Kehr, Sandrine Coquille, Joop van den Heuvel, Clemens Steegborn, Makoto Fushimi, Efrat Finkin-Groner, Robert W. Myers, Stacia Kargman, Nigel J. Liverton, David J. Huggins, Peter T. Meinke
Summary: Soluble adenylyl cyclase is an enzyme involved in intracellular signaling, and it plays a crucial role in male fertility. Evaluation of sAC inhibitors provides essential information for the development of male contraceptives.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Shan Sun, Makoto Fushimi, Thomas Rossetti, Navpreet Kaur, Jacob Ferreira, Michael Miller, Jonathan Quast, Joop van den Heuvel, Clemens Steegborn, Lonny R. Levin, Jochen Buck, Robert W. Myers, Stacia Kargman, Nigel Liverton, Peter T. Meinke, David J. Huggins
Summary: Free energy perturbation is used to predict the effects of small changes to an inhibitor structure on the binding free energy. This paper focuses on its utility in the hit-to-lead stage of a drug discovery project targeting soluble adenyl cyclase. X-ray crystallography was used throughout the project to enable structural analysis. The results demonstrate that free energy perturbation can facilitate the rapid progress of a drug discovery campaign, enabling proof-of-concept studies for target validation.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Ophthalmology
Shakarr V. V. Wiggins, Ryan Schreiner, Jacob Ferreira, Alan D. D. Marmorstein, Lonny R. R. Levin, Jochen Buck
Summary: This study investigated whether a clinically used carbonic anhydrase inhibitor (CAIs) can modulate intraocular pressure (IOP) through soluble adenylyl cyclase (sAC) signaling. IOP was measured 1 h after topical treatment with brinzolamide, a topically applied and clinically used CAIs, using direct cannulation of the anterior chamber in sAC knockout (KO) mice or C57BL/6J mice in the presence or absence of the sAC inhibitor (TDI-10229). The results showed that mice treated with the sAC inhibitor TDI-10229 had elevated IOP. On the other hand, CAIs treatment significantly decreased increased IOP in wild-type, sAC KO mice, as well as TDI-10229-treated mice. These findings suggest that inhibiting carbonic anhydrase reduces IOP independently from sAC in mice, and brinzolamide regulates IOP through a signaling cascade that does not involve sAC.
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
(2023)
Review
Biology
Tom Rossetti, Stephanie Jackvony, Jochen Buck, Lonny R. Levin
Summary: Soluble adenylyl cyclase (sAC) is a bicarbonate-regulated enzyme that acts as a sensor for HCO3-/CO2/pH, regulating diverse physiological functions.
Article
Ophthalmology
Mohammad Shahidullah, Amritlal Mandal, Guojun Wei, Lonny R. Levin, Jochen Buck, Nicholas A. Delamere
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2014)
