Review
Endocrinology & Metabolism
Hari Prasad, John Kandam Kulathu Mathew, Sandhya S. Visweswariah
Summary: This review highlights the importance of Receptor Guanylyl Cyclase C (GC-C) in regulating intestinal fluid and ion homeostasis, and its causal link to intestinal inflammation, dysbiosis, and tumorigenesis. The GC-C signaling pathway plays a role in extra gastrointestinal functions such as appetite control, energy expenditure, visceral nociception, and behavioral processes. Recent research has also uncovered the involvement of GC-C in the ion-microbiome-immune axis in inflammatory bowel disease and suggests potential therapeutic strategies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nitzan Tal, Benjamin R. Morehouse, Adi Millman, Avigail Stokar-Avihail, Carmel Avraham, Taya Fedorenko, Erez Yirmiya, Ehud Herbst, Alexander Brandis, Tevie Mehlman, Yaara Oppenheimer-Shaanan, Alexander F. A. Keszei, Sichen Shao, Gil Amitai, Philip J. Kranzusch, Rotem Sorek
Summary: This study identifies the roles of cyclic pyrimidines cCMP and cUMP as immunity signaling molecules in bacterial defense against viruses. A family of bacterial pyrimidine cyclase enzymes was discovered to specifically synthesize these molecules following phage infection, activating immune effectors for antiviral response. Defense systems encoding pyrimidine cyclases, known as Pycsar, are widespread in prokaryotes, providing a clear biological function for cCMP and cUMP in bacterial immunity.
Article
Multidisciplinary Sciences
Yue Dai, Emily M. Faul, Arnab Ghosh, Dennis J. Stuehr
Summary: Nitric oxide (NO) signaling in biology relies on its activating cyclic guanosine monophosphate (cGMP) production by the NO receptor soluble guanylyl cyclase (sGC). Physiological levels of NO trigger the mobilization of heme to immature sGC, leading to the construction of functional sGC heterodimers and increased active sGC levels. The process involves glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-heme complexes and the chaperone hsp90.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Multidisciplinary Sciences
Se-Min Kim, Tony Yuen, Jameel Iqbal, Mishaela R. Rubin, Mone Zaidi
Summary: The NO-cGMP-PKG pathway is crucial for skeletal homeostasis, but long-term use of NO is limited by off-target effects. Inhibiting cGMP-specific phosphodiesterase to promote the anabolic signal offers a potential treatment for osteoporosis with PDE5A inhibitors. Further research is needed to investigate the specific effects of PDE5A inhibition on bone cells and the pathophysiological changes in skeletal PDE5A expression.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Maryam Alapa, Chuanlong Cui, Ping Shu, Hong Li, Vlad Kholodovych, Annie Beuve
Summary: The study found that redox modifications play a crucial role in NO activation of GC1, with NO-stimulated GC1 containing more bound Cys, potentially disulfide bonds. Mass spectrometry identified ten oxidized and two reduced Cys in NO-stimulated GC1, and computational modeling narrowed down potential Cys candidates involved in disulfide bonds to Cys489 and Cys571. Mutational studies confirmed the involvement of Cys489 and Cys571 in GC1's response to NO, potentially as a thiol/disulfide switch.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biology
Yuehui Tian, Georg Nagel, Shiqiang Gao
Summary: By exchanging gene segments, Cop5 from Chlamydomonas reinhardtii can produce a bistable guanylyl cyclase that can switch its activity through short dark light flashes.
Article
Physiology
Malte Verheyen, Michelle Puschkarow, Stefanie Gnipp, Doris Koesling, Marcus Peters, Evanthia Mergia
Summary: In this study, we investigated the role of NO-GC isoforms in respiration by measuring lung function parameters of isoform-specific knockout mice. Our findings suggest that NO-GC1-derived cGMP plays a significant role in regulating airway tone, while NO-GC2 affects tissue elasticity and airway reactivity.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Joseph C. Galley, Megan P. Miller, Subramaniam Sanker, Mingjun Liu, Iraida Sharina, Emil Martin, Delphine Gomez, Adam C. Straub
Summary: This study identifies Forkhead box subclass O protein 4 (FoxO4) as a key transcriptional regulator of GUCY1B3 expression, coding for sGC13 protein in human and animal smooth muscle cells (SMCs). This discovery may have important implications for future antihypertensive and vasodilatory therapies targeting NO production, sGC, or FoxO transcription factors.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chien-Wei Chen, Luen-Kui Chen, Tai-Ying Huang, De-Ming Yang, Shui-Yu Liu, Pei-Jiun Tsai, Tien-Hua Chen, Heng-Fu Lin, Chi-Chang Juan
Summary: Plasma and tissue zinc ion levels are associated with obesity development. NO treatment stimulates intracellular Zn2+ mobilization through the GC/cGMP/PKG pathway, subsequently stimulating adipocyte differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Iraida Sharina, Karina Lezgyieva, Yekaterina Krutsenko, Emil Martin
Summary: This study characterized a rare sGC variant with reduced cGMP-forming activity, high susceptibility to oxidative stress, and diminished protein stability. These deficiencies contribute to the severity of moyamoya disease and achalasia symptoms in carriers of this variant.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Gang Wu, Iraida Sharina, Emil Martin
Summary: Nitric oxide (NO), carbon monoxide (CO), oxygen (O-2), and hydrogen sulfide (H2S) are gaseous molecules that play important roles in the physiology and pathophysiology of eukaryotes. Soluble guanylyl cyclase (sGC), a hemoprotein, acts as a sensor and transducer for these gases, as well as a transporter.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Endocrinology & Metabolism
Brandon M. Wagner, Jerid W. Robinson, Timothy C. R. Prickett, Eric A. Espiner, Sundeep Khosla, Dana Gaddy, Larry J. Suva, Lincoln R. Potter
Summary: C-type natriuretic peptide (CNP) activates guanylyl cyclase-B (GC-B) to catalyze the synthesis of cGMP, which affects bone length and mass. GC-B mutant mice with increased CNP-dependent GC-B activity show increased bone length, mass, and strength. However, the mechanism by which GC-B increases bone mass remains unknown.
CALCIFIED TISSUE INTERNATIONAL
(2022)
Article
Biology
Paul Fischer, Shatanik Mukherjee, Enrico Peter, Matthias Broser, Franz Bartl, Peter Hegemann
Summary: Enzymerhodopsins are a newly discovered class of rhodopsins, including several different types such as histidine kinase rhodopsin, rhodopsin phosphodiesterases, and rhodopsin guanylyl cyclases (RGCs). The regulatory influence of the rhodopsin domain on enzyme activity remains partially understood, but is crucial for a deeper understanding of intra-molecular signaling pathways. By studying the light-induced dynamics of a RGC from the Catenaria anguillulae fungus, researchers gained insights into the catalytic process and structural rearrangements upon photo-activation of the protein.
Article
Biochemistry & Molecular Biology
Maria Duszyn, Brygida Swiezawska-Boniecka, Aloysius Wong, Krzysztof Jaworski, Adriana Szmidt-Jaworska
Summary: Recent studies identified a novel receptor BdPepR2 in Brachypodium distachyon, showing both catalytic and kinase activity, with important implications for plant processes. Through bioinformatic analysis, a conserved core catalytic motif was designed, leading to the discovery of potential GCs in monocots.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Susana S. Correia, Rajesh R. Iyengar, Peter Germano, Kim Tang, Sylvie G. Bernier, Chad D. Schwartzkopf, Jenny Tobin, Thomas W. -H. Lee, Guang Liu, Sarah Jacobson, Andrew Carvalho, Glen R. Rennie, Joon Jung, Paul A. Renhowe, Elisabeth Lonie, Christopher J. Winrow, John R. Hadcock, Juli E. Jones, Mark G. Currie
Summary: Effective treatments for neurodegenerative diseases are urgently needed as the global population ages. CY6463, a brain-penetrant sGC stimulator, has shown promise in preclinical models by improving neuronal activity, mediating neuroprotection, and enhancing cognitive performance.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hari Prasad, Avinash Ravindranath Shenoy, Sandhya Srikant Visweswariah
Article
Biochemistry & Molecular Biology
Sintu Samanta, Priyanka Biswas, Arka Banerjee, Avipsa Bose, Nida Siddiqui, Subhalaxmi Nambi, Deepak Kumar Saini, Sandhya S. Visweswariah
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Review
Biochemistry & Molecular Biology
Avipsa Bose, Sanghita Banerjee, Sandhya S. Visweswariah
Review
Chemistry, Multidisciplinary
Pradeep Sathyanarayana, Sandhya S. Visweswariah, K. Ganapathy Ayappa
Summary: Pore forming toxins are the largest class of bacterial toxins, designed to form nanochannels in target cell membranes and causing cell death. Understanding the complex conformational changes and oligomerization pathways of these toxins is crucial for designing intervention strategies and specialized technologies.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Biophysics
Anisha Zaveri, Avipsa Bose, Suruchi Sharma, Abinaya Rajendran, Priyanka Biswas, Avinash R. Shenoy, Sandhya S. Visweswariah
Summary: Mycobacteria possess a unique class of adenylyl cyclases with complex domain organization, including gene pairs where one member is a pseudoenzyme and the other binds adenine nucleotides and DNA/RNA in a sequence-independent manner, forming bio-crystallized nucleoids under specific conditions. These enzymes exhibit unusual biochemical properties that warrant further investigation into their physiological roles.
BIOPHYSICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Sohini Chakraborti, Moubani Chakraborty, Avipsa Bose, Narayanaswamy Srinivasan, Sandhya S. Visweswariah
Summary: The emergence of multidrug-resistant and extensively drug-resistant tuberculosis poses a significant challenge to TB treatment, necessitating the search for novel therapeutic strategies. This study utilized the cAMP-bound crystal structure of Mtb USP (Rv1636) to identify potential binders through molecular docking, providing initial guidance for the synthesis and testing of compounds with the potential to inhibit Mtb USP (Rv1636) for the development of novel antitubercular lead candidates.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Review
Gastroenterology & Hepatology
Hari Prasad, Sandhya S. Visweswariah
Summary: This review discusses the importance of impaired sodium transport in the pathogenesis of inflammatory bowel disease (IBD) and the underlying genetic mutations. It proposes that impaired sodium transport may be an upstream pathogenic factor in the development of IBD, and explores how sodium malabsorption affects downstream pathophysiology. Further research into salt and water transport mechanisms in the intestine may provide new insights into the interaction between ions, the microbiome, and the immune system in driving IBD.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Article
Immunology
Vishwas Mishra, Avipsa Bose, Shashi Kiran, Sanghita Banerjee, Idrees A. Shah, Pooja Chaukimath, Mudasir M. Reshi, Swarna Srinivas, Anaxee Barman, Sandhya S. Visweswariah
Summary: Activation mutations in receptor guanylyl cyclase C (GC-C) lead to early-onset diarrhea and chronic inflammatory bowel disease. A new mouse model with an activating mutation in Gucy2c showed increased intestinal cGMP levels and susceptibility to colitis, providing insights into the role of cGMP in gut inflammation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Correction
Immunology
Vishwas Mishra, Avipsa Bose, Shashi Kiran, Sanghita Banerjee, Idrees A. Shah, Pooja Chaukimath, Mudasir M. Reshi, Swarna Srinivas, Anaxee Barman, Sandhya S. Visweswariah
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Preeti Sharma, Anjali Vijaykumar, Jayashree Vijaya Raghavan, Supriya Rajendra Rananaware, Alakesh Alakesh, Janhavi Bodele, Junaid Ur Rehman, Shivani Shukla, Virta S. Wagde, Savitha Nadig, Sveta Chakrabarti, Sandhya S. Visweswariah, Dipankar Nandi, Balasubramanian Gopal, Siddharth Jhunjhunwala
Summary: This study demonstrates that the uptake of non-stimulatory cargo-free particles enhances the phagocytic ability of immune cells. The increased phagocytosis is driven by changes in cell membrane fluidity and cellular compliance, and it leads to faster neutralization of pathogens and clearance in mice.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Biochemistry & Molecular Biology
Akshat Joshi, Saswat Choudhury, Sriram Bharath Gugulothu, Sandhya S. Visweswariah, Kaushik Chatterjee
Summary: In recent years, significant advancements have been made in three-dimensional (3D) printing techniques for scaffold fabrication. However, the lack of strategies to promote vascularization in 3D printed scaffolds has limited their performance and host integration. Researchers are exploring various approaches to enhance vascularization in 3D printed scaffolds, aiming to improve scaffold functionality and ensure optimal integration with the host.
Article
Oncology
Imran Khan, Brunilde Gril, Ayuko Hoshino, Howard H. Yang, Maxwell P. Lee, Simone Difilippantonio, David C. Lyden, Patricia S. Steeg
Summary: This study demonstrates that tumor-derived exosomes can suppress metastasis by delivering the NME1 metastasis suppressor to recipient tumor cells, resulting in altered endocytic patterns and reduced cell motility and migration. Proteomic analysis of the exosomes identified differentially expressed proteins that may contribute to these effects. Liposomes containing rNME1 also exhibited similar suppressive effects. These findings expand our understanding of the functions of exosomes and liposomes and provide a novel approach to prevent metastasis.
CLINICAL & EXPERIMENTAL METASTASIS
(2022)
Review
Biochemistry & Molecular Biology
Pooja Chaukimath, Gad Frankel, Sandhya S. Visweswariah
Summary: Bacterial infections of the gut are a major cause of worldwide morbidity and mortality. This review focuses on the interplay between pathogens and the host in the gut, with pathogens evolving to establish infection while the host mounts a response to eliminate the infection. The review also highlights how gut pathogens manipulate host metabolism and describes host responses to the infection.
Article
Genetics & Heredity
Kriti Gupta, Sveta Chakrabarti, Vishnu Janardan, Nishita Gogia, Sanghita Banerjee, Swarna Srinivas, Deepthi Mahishi, Sandhya S. Visweswariah
Summary: This article describes the multiple roles of a previously uncharacterized metallophosphodiesterase in Drosophila, including regulation of immune pathways, lifespan, perception ability, and sensitivity to odorants. Further studies revealed similarities between this gene product and the mammalian gene MPPED2, which is associated with WAGR syndrome.
Article
Cell Biology
Sveta Chakrabarti, Sandhya S. Visweswariah