Review
Cell Biology
Yoichiro Kamimura, Masahiro Ueda
Summary: Chemotaxis is the process of cells undergoing directional movement along ambient chemical gradients, playing important roles in human physiology and pathology. Studies on Dictyostelium cells have elucidated the crucial roles of various mechanisms of GPCR signaling in broad range sensing of chemical gradients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Developmental Biology
Farah Saad, David R. Hipfner
Summary: The Hedgehog (Hh) pathway is regulated by G protein-coupled receptors (GPCRs) in Drosophila, with Mthl5 identified as a modulator of this pathway. This suggests potential crosstalk between GPCRs and the Hh pathway in mammals as well.
Article
Genetics & Heredity
Jennifer E. Jenkins, Rachel H. Roberts-Galbraith
Summary: G protein-coupled receptors (GPCRs) play important roles in development and stem cell biology. However, their functions in complex tissue regeneration are not well understood. In this study, we investigated the roles of GPCRs and downstream signal transducers in planarian flatworms, which can regenerate all tissues. Our findings suggest that heterotrimeric G proteins, specifically G alpha q1 and G beta 1-4a, promote the late phase of anterior polarity reestablishment during regeneration. Additionally, we identified a serotonin receptor, gcr052, that works with G alpha s2 and G beta x2 in planarian locomotion.
Review
Cell Biology
Preeti Kumari Chaudhary, Soochong Kim
Summary: GPCRs play a crucial role in cancer progression, but the specific mechanisms of their involvement are still unclear. Studies have revealed the multifaceted impact of GPCRs on cancer development and the signaling pathways involved.
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Physiology
Davide Calebiro, Zsombor Koszegi, Yann Lanoiselee, Tamara Miljus, Shannon O'Brien
Summary: Recent research has revealed transient interactions between GPCRs and G proteins in living cells, resulting in short-lived signaling nanodomains that may confer rapidity and specificity to signal transduction. These findings could potentially offer new strategies for modulating GPCR function and pave the way for innovative drug development for common diseases like diabetes or heart failure.
PHYSIOLOGICAL REVIEWS
(2021)
Review
Chemistry, Medicinal
Hyeonyeong Im, Ji-Hyun Park, Seowoo Im, Juhyeong Han, Kyungmin Kim, Yun-Hee Lee
Summary: The high incidence of obesity has led to an increased need to discover new therapeutic targets. Recent research has shown that G-protein coupled receptors (GPCRs) could be potential therapeutic targets to regulate adipose tissue metabolism.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Biology
Alexander S. Hauser, Charlotte Avet, Claire Normand, Arturo Mancini, Asuka Inoue, Michel Bouvier, David E. Gloriam
Summary: Two-thirds of human hormones and one-third of clinical drugs act on membrane receptors coupled to G proteins, but there are differences in the reported G protein couplings among recent large-scale datasets. This study presents a common coupling map that uncovers novel couplings, GPCR-G protein selectivity, and the comparison of co-coupling and co-expression of G proteins with phylogenetic relationships. These findings will advance receptor research and cellular signaling, and contribute to the development of safer drugs.
Review
Cell Biology
Haichang Luo, Ezequiel Marron Fernandez de Velasco, Kevin Wickman
Summary: G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels play a critical inhibitory role in neurons. They are regulated by G proteins, phosphatidylinositol 4,5-bisphosphate (PIP2), phosphorylation, regulator of G protein signaling (RGS) proteins, as well as intracellular Na+ and Ca2+. Various stimuli can modify neuronal GIRK channel activity transiently or persistently, including exposure to drugs of abuse, changes in neuronal activity patterns, and aversive experience. Dysregulation of GIRK channel activity has been implicated in neurological diseases and disorders.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Stephane Angers
Summary: This study reveals a Wnt-stimulated positive feedback loop involving local production and recruitment of PI(4,5)P-2 to facilitate LRP5/6 phosphorylation.
Article
Multidisciplinary Sciences
Jingyi Zhao, Vincent DiGiacomo, Mariola Ferreras-Gutierrez, Shiva Dastjerdi, Alain Ibanez de Opakua, Jong-Chan Park, Alex Luebbers, Qingyan Chen, Aaron Beeler, Francisco J. Blanco, Mikel Garcia-Marcos
Summary: IGGi-11 selectively inhibits noncanonical activation of heterotrimeric G-protein signaling, blocking tumor cell signaling and inhibiting metastatic cancer cell invasion without interfering with canonical GPCR signaling mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Plant Sciences
Genki Chaya, Shuhei Segami, Moeka Fujita, Yoichi Morinaka, Yukimoto Iwasaki, Kotaro Miura
Summary: This study reveals that both DEP1 and OsGGC2 genes are positive regulators of plant height and their functions are redundant.
Article
Endocrinology & Metabolism
Mahvash A. Goolam, Alice P. Brown, Kimberly T. Edwards, Karen J. Gregory, Katie Leach, Arthur D. Conigrave
Summary: The calcium-sensing receptor plays a crucial role in regulating human calcium and mineral metabolism by sensing extracellular Ca2+. Mutations in the receptor can impair its function and calcium sensitivity, and receptor asymmetry may contribute to the underlying mechanisms.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Cell Biology
Pablo Astudillo
Summary: This study analyzed the role of the Wnt signaling pathways in gastric cancer and identified a WNT5A/FZD2/FZD7/ROR2 signature associated with tumor-infiltrating and mesenchymal cell marker expression. High expression of FZD7 and ROR2 correlated with a shared gene and protein expression profile, which in turn correlated with poor prognosis. Overall, the findings provide an updated perspective on the contributions of the Wnt/beta-catenin and non-canonical Wnt pathways in gastric cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Francesca Manuela Johnson de Sousa Brito, Andrew Butcher, Addolorata Pisconti, Blandine Poulet, Amanda Prior, Gemma Charlesworth, Catherine Sperinck, Michele Scotto di Mase, Ke Liu, George Bou-Gharios, Robert Jurgen van 't Hof, Anna Daroszewska
Summary: Syndecan-3 promotes new bone formation in osteoblasts by enhancing WNT signaling, and its deficiency in mice results in an early osteoporosis-like phenotype due to delayed osteoblast maturation and impaired function. Overexpressing Sdc3 in osteoblasts rescues the low bone volume phenotype and increases bone mass, making SDC3 a potential target for novel bone anabolic drug development.
Review
Pharmacology & Pharmacy
Yonika Larasati, Cedric Boudou, Alexey Koval, Vladimir L. Katanaev
Summary: The Wnt signaling pathway plays a critical role in carcinogenesis, and FZD(7) receptor is important in various cancers. This review summarises the functions of FZD(7) in carcinogenesis and tissue homeostasis, discusses the development of drugs targeting FZD(7), and explores the challenges and possibilities in developing FZD(7)-selective antagonists.
DRUG DISCOVERY TODAY
(2022)
Article
Multidisciplinary Sciences
Cezanne Miete, Gonzalo P. Solis, Alexey Koval, Martina Bruckner, Vladimir L. Katanaev, Jurgen Behrens, Dominic B. Bernkopf
Summary: This study finds that G alpha i2 can induce the condensation of conductin, leading to the degradation of β-catenin and inhibition of Wnt signaling, thus suppressing the growth of colorectal cancer. Colorectal cancer evades this inhibition by decreasing the expression of G alpha i2 and inactivating mutations, but the G alpha i2-activating drug guanabenz can reduce colorectal cancer growth.
NATURE COMMUNICATIONS
(2022)
Article
Plant Sciences
Robin Huber, Laurence Marcourt, Alexey Koval, Sylvain Schnee, Davide Righi, Emilie Michellod, Vladimir L. Katanaev, Jean-Luc Wolfender, Katia Gindro, Emerson Ferreira Queiroz
Summary: A series of complex phenylpropanoid derivatives were obtained by chemoenzymatic biotransformation. These compounds showed anti-Wnt activity and have potential applications.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Neurosciences
Denis Silachev, Alexey Koval, Mikhail Savitsky, Guru Padmasola, Charles Quairiaux, Fabrizio Thorel, Vladimir L. Katanaev
Summary: This study establishes two mouse models of GNAO1 encephalopathy, which simulate different clinical manifestations of the disease and reveal it as a neurodevelopmental disorder. These models contribute to understanding the disease mechanism and developing future treatment approaches.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Antonina Klimenko, Robin Huber, Laurence Marcourt, Dmitry Tabakaev, Alexey Koval, Salim Sh. Dautov, Tatyana N. N. Dautova, Jean-Luc Wolfender, Rob Thew, Yuri Khotimchenko, Emerson Ferreira Queiroz, Vladimir L. L. Katanaev
Summary: Through metabolite analysis, we have identified five new chlorin compounds from Ophiura sarsii and O. ooplax, demonstrating their potential applications in photodynamic therapy.
Review
Biochemistry & Molecular Biology
Vladimir L. Katanaev, Alexey Baldin, Tatiana V. Denisenko, Denis N. Silachev, Anna E. Ivanova, Gennadiy T. Sukhikh, Lee Jia, Lev A. Ashrafyan
Summary: Wnt signaling plays multiple important roles in cancer, including primary transformation, tumor growth, and metastasis. It is not only crucial for cancer cell-intrinsic functions but also for cross-communication among different cell types in the tumor microenvironment. Various cell types, such as fibroblasts, macrophages, endothelial cells, and lymphocytes, use the Wnt language to communicate with cancer cells and each other, and these messages are essential for tumor progression and fate. Decoding this language will provide valuable insights into tumor biology and lead to novel therapeutic strategies.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Vladimir L. Katanaev
Summary: Neuroscience and neurology research heavily relies on experimentation with rodents, but non-vertebrate models such as fruit flies have not been able to fully replace mice and rats in these studies. One reason is that existing methodologies for creating fruit fly models of neurological diseases do not accurately reflect the genetic conditions of the diseases. Therefore, the author argues for a systematic humanization approach, where the fruit fly orthologs of human disease genes are replaced with the human sequences. This approach would improve disease modeling and drug discovery in fruit flies.
ANIMAL MODELS AND EXPERIMENTAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Alexey Koval, Yonika A. Larasati, Mikhail Savitsky, Gonzalo P. Solis, Jean-Marc Good, Mathieu Quinodoz, Carlo Rivolta, Andrea Superti-Furga, Vladimir L. Katanaev
Summary: A study found a mutation in the GNAO1 gene associated with pediatric encephalopathies. A precision medicine workflow combining NGS diagnostics, molecular etiology analysis, and personalized drug discovery was used to study this mutation. The mutation was found to cause structural changes in the Gao protein, leading to aberrant biochemical functions and providing insights into the molecular etiology of this pathology.
Article
Microbiology
Alexey Koval, Jiabin Xu, Nathalia Williams, Mirco Schmolke, Karl-Heinz Krause, Vladimir L. Katanaev
Summary: Despite previous indications, pharmacological modulation of the Wnt pathway is not a promising strategy to control SARS-CoV-2 infection in lung epithelia.
MICROBIOLOGY SPECTRUM
(2023)
Article
Multidisciplinary Sciences
Alexey Koval, Xin Zhang, Vladimir L. Katanaev
Summary: Intracellular signaling plays crucial roles in an organism's development and functioning, and dysregulation of signaling pathways can lead to various pathologies, including cancer. A key characteristic of cell signaling is channel capacity, which measures how much information can be reliably transmitted by a signaling system. In this study, we present improved methods to quantify the channel capacity of GPCR signaling in single cells, and we analyze the channel capacity of cancer cells for the first time. We find that different types of cancer cells exhibit decreased channel capacity in their GPCR signaling, supporting the hypothesis that cancer is an information disease. These findings have important implications for understanding cancer biology and discovering new anticancer drugs.
Meeting Abstract
Plant Sciences
R. Huber, L. Marcourt, A. Luscher, A. Koval, N. Hanna, J. Nitschke, S. Schnee, E. Michellod, T. Kohler, V. L. Katanaev, T. Soldati, J-L Wolfender, K. Gindro, Queiroz E. Ferreira
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)
