Review
Neurosciences
Rameshwar K. K. Sharma
Summary: This article reviews the history of the membrane guanylate cyclase (MGC) development from 1963 to 1987. It highlights the effort and continuous work that led to the establishment of this critical cellular signaling pathway for the survival of prokaryotes, eukaryotes, and complex vertebrate organisms.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Giovanni Caruso, Colin Klaus, Heidi E. Hamm, Vsevolod V. Gurevich, Paolo Bisegna, Daniele Andreucci, Emmanuele DiBenedetto, Clint L. Makino
Summary: Retinal rods have evolved to detect single photons and function over a wide range of light intensities. Various processes within these cells enable them to adapt to different levels of illumination. By adding certain mechanisms to an existing biophysical model, the authors were able to explain the response of rod cells under high light levels. The model accurately described the behavior of both wild-type and mutant rods and provided insights into the saturation dynamics.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Review
Cardiac & Cardiovascular Systems
Alexandra Petraina, Cristian Nogales, Thomas Krahn, Hermann Mucke, Thomas F. Luscher, Rodolphe Fischmeister, David A. Kass, John C. Burnett, Adrian J. Hobbs, Harald H. H. W. Schmidt
Summary: Mechanism-based therapy focused on understanding disease pathways at the molecular level is still rare in cardiovascular medicine, but recent drug developments centered around cGMP offer promising personalized treatment options. By modulating cGMP synthesis or breakdown, these drugs show potential for protective effects across various cardiac conditions.
CARDIOVASCULAR RESEARCH
(2022)
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
Microbiology
Stephanie D. Nofal, Avnish Patel, Michael J. Blackman, Christian Flueck, David A. Baker
Summary: Guanylyl cyclases synthesize cyclic GMP, which plays a critical role in regulating cellular functions. In malaria parasites, GCs are associated with a unique bifunctional domain. The study shows that Plasmodium falciparum GC alpha is essential for cGMP production and merozoite egress, with the P4-ATPase domain playing a primary role in cGMP synthesis.
Review
Neurosciences
Teresa Duda, Rameshwar K. Sharma
Summary: One monumental discovery in cell biology is the establishment of the membrane guanylate cyclase signal transduction system, which revolutionized therapy development and has implications for atmospheric carbon dioxide. This review provides an historical account of their evolutionary development and mechanisms of interaction.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Ilona Turek, Lubna Freihat, Jignesh Vyas, Janet Wheeler, Victor Muleya, David T. Manallack, Chris Gehring, Helen Irving
Summary: Recent discoveries have identified low-activity guanylate cyclase (GC) catalytic centers within kinase domains in plants, which generate cGMP essential for intramolecular and downstream signaling. Researchers have explored the existence of such cryptic GCs in human proteome and found 18 candidates, including the neurotropic receptor tyrosine kinase 1 (NTRK1). In vitro studies revealed that the embedded NTRK1 GC is functional and exhibits a preference for Mn2+ over Mg2+. These findings suggest previously unsuspected roles of cGMP in intramolecular and downstream signaling of NTRK1, as well as its involvement in NTRK1-dependent growth and neoplasia.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Chad D. Schwartzkopf, John R. Hadcock, Guang Liu, Peter Germano, Julien Roux, Courtney M. Shea, Emmanuel S. Buys, Juli E. Jones
Summary: Praliciguat treatment showed metabolic effects of increasing energy utilization, improving insulin sensitivity, and reducing plasma triglycerides in diet-induced obesity (DIO) mice.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Avesani, Laura Bielefeld, Nicole Weisschuh, Valerio Marino, Pascale Mazzola, Katarina Stingl, Tobias B. Haack, Karl-Wilhelm Koch, Daniele Dell'Orco
Summary: This study characterizes the biochemical and biophysical properties of human GCAP3 and identifies a mutation in GUCA1C that may contribute to retinitis pigmentosa.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Cameron Lee-Lopez, Erik Yukl
Summary: Nitric oxide (NO) is a toxic gas that can affect bacterial behavior in non-toxic concentrations, especially in the transition between planktonic and biofilm-associated lifestyles. Heme nitric oxide/oxygen binding proteins (H-NOX) are a family of bacterial sensors that regulate biofilm formation in response to NO. The role of H-NOX in pathogenesis is still unclear but it may play a role in regulating biofilm formation and persistence in the environment.
BIOSCIENCE REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Dominique E. Williams, Natasha M. Nesbitt, Sandhya Muralidharan, Sajjad Hossain, Elizabeth M. Boon
Summary: Transitions between motile and biofilm lifestyles are regulated by H-NOX, a key regulator of bacterial communal behaviors. In Agrobacterium vitis S4, avH-NOX binds to and regulates the activity of avHaCE, a predicted bifunctional cyclic di-GMP metabolizing enzyme. avH-NOX enhances cyclic di-GMP degradation to reduce biofilm formation in response to NO in A. vitis.
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
Neurosciences
Rajan D. Adhikari, Amanda M. Kossoff, M. Carter Cornwall, Clint L. Makino
Summary: Rod photoreceptors in the retina adjust their responsiveness and sensitivity to different light intensities. Bicarbonate increases the dark current and accelerates flash response kinetics in amphibian rods. In mice, bicarbonate increases the dark current, absolute sensitivity, and flash response recovery in rods to a greater extent than in amphibian rods, and enables them to respond to dimmer flashes.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Garyfallia I. Makrynitsa, Aikaterini I. Argyriou, Aikaterini A. Zompra, Konstantinos Salagiannis, Vassiliki Vazoura, Andreas Papapetropoulos, Stavros Topouzis, Georgios A. Spyroulias
Summary: This study investigated the interaction of sGC stimulator BAY 41-2272 with Ns H-NOX, mapped the amino acids mediating this interaction, and provided evidence to explain the characteristic synergy of BAY 41-2272 with NO.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Microbiology
Courtney N. Dial, Lauren Speare, Garrett C. Sharpe, Scott M. Gifford, Alecia N. Septer, Karen L. Visick
Summary: Vibrio fischeri efficiently colonizes its squid host by producing a transient biofilm dependent on symbiosis polysaccharide. Yeast extract inhibits biofilm formation, while omitting it and adding vitamin pABA and calcium can induce biofilm formation. pABA increases the concentration of c-di-GMP, which plays a crucial role in inducing biofilm formation.