Article
Biochemistry & Molecular Biology
Jong-Chan Park, Alex Luebbers, Maria Dao, Ana Semeano, Anh Minh Nguyen, Maria P. Papakonstantinou, Stefan Broselid, Hideaki Yano, Kirill A. Martemyanov, Mikel Garcia-Marcos
Summary: In this study, researchers uncover a new mechanism of G protein regulation involving the protein GINIP, which biases inhibitory GPCR responses towards Gbg signaling and dampens Gai-GTP signaling. This mechanism is crucial for maintaining balanced neurotransmission and preventing increased seizure susceptibility in mice.
Article
Biochemistry & Molecular Biology
Donghoon Ahn, Donghee Ham, Ka Young Chung
Summary: In recent years, deeper insights into the stepwise conformational changes during GPCR-G protein coupling have been obtained using various techniques such as hydrogen/deuterium exchange mass spectrometry, hydroxyl radical footprinting-mass spectrometry, X-ray crystallography, cryoelectron microscopy, and molecular dynamics simulation.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Dinesh Kankanamge, Mithila Tennakoon, Ajith Karunarathne, N. Gautam
Summary: This review focuses on the current knowledge about the potential roles and mechanisms of the gamma subunits of heterotrimeric G proteins. Loss or dysregulation of specific gamma subunit types can result in different phenotypes and even cancers. Imaging studies have revealed that the membrane affinity of gamma subunits controls the sensitivity and adaptation of cells to external signals.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
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
Biochemistry & Molecular Biology
Naincy R. Chandan, Saji Abraham, Shuvasree SenGupta, Carole A. Parent, Alan Smrcka
Summary: G protein-coupled receptors (GPCRs) play a crucial role in regulating cell and tissue physiology. Through proteomics analysis, researchers identified proteins that interact with the active form of G alpha(i) protein and discovered that one of these proteins, PDZ-RhoGEF (PRG), is stimulated by active G alpha(i). Further experiments revealed that active G alpha(i) regulates the polarization of phosphorylated myosin light chain, a process critical for cell migration, by activating PRG.
Article
Pharmacology & Pharmacy
Masaki Saito, Ayano Chiba, Takeya Sato, Takahiro Moriya, Jun Sukegawa, Norimichi Nakahata
Summary: Proteins interacting with G protein-coupled receptors can modulate signal transduction, and in this study, Tctex-1 was found to enhance PTHR-mediated signaling by activating adenylyl cyclase. Additionally, Tctex-1 was shown to directly bind to AC type 6, revealing a novel mechanism of GPCR/G(s) signaling regulation by Tctex-1.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2021)
Article
Cell Biology
Brian S. Muntean, Ikuo Masuho, Maria Dao, Laurie P. Sutton, Stefano Zucca, Hideki Iwamoto, Dipak N. Patil, Dandan Wang, Lutz Birnbaumer, Randy D. Blakely, Brock Grill, Kirill A. Martemyanov
Summary: The study demonstrates that G protein alpha subunit o plays a crucial role in the nervous system by modulating neuromodulatory signals in striatal neurons, essential for motor control. Pathogenic mutations in its gene are shown to alter G alpha o function in a neuron-type specific manner, affecting movement disorders.
Article
Pharmacology & Pharmacy
Carolina Montanez-Miranda, Riley E. Perszyk, Nicholas H. Harbin, Jennifer Okalova, Suneela Ramineni, Stephen F. Traynelis, John R. Hepler
Summary: Regulators of G protein signaling (RGS) proteins have been associated with various diseases, including cancers, but the impact of mutations on protein function is unclear. Using a new bioinformatic tool (3DMTR), researchers analyzed the RGS domains of 15 RGS protein family members and found that certain cancer-related mutations resulted in functional changes that affect GPCR-G protein signaling activity. This suggests that 3DMTR is a potentially useful bioinformatics tool for predicting functionally important protein residues.
MOLECULAR PHARMACOLOGY
(2023)
Review
Medicine, Research & Experimental
Juan Carlos Martinez-Morales, K. Helivier Solis, M. Teresa Romero-Avila, Guadalupe Reyes-Cruz, J. Adolfo Garcia-Sainz
Summary: G protein-coupled receptors (GPCRs) are membrane proteins that function as sensors and play significant roles in various physiological and pathological processes. This review provides an overview of the current understanding of the structure, signaling, internalization, and recycling of GPCRs.
ARCHIVES OF MEDICAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Sonia Munoz-Lopez, Alejandro Sanchez-Melgar, Mairena Martin, Jose Luis Albasanz
Summary: Despite the lack of effective treatment for cancer, natural compounds such as resveratrol have shown promise in cancer therapy. Resveratrol can modulate various signaling pathways related to cancer initiation and progression. This study investigates the impact of resveratrol treatment on adenosinergic pathway components and cell viability in HeLa and SH-SY5Y cell lines, revealing changes in the pathway that may contribute to the anti-tumoral effects of resveratrol.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maozhen Luo, Zhiwei Han, Guoye Huang, Rongfang Li, Yi Liu, Junjie Lu, Lin Liu, Rui Miao
Summary: In this review, the structural characteristics of guanine nucleotide-binding (G) proteins and their binding modes with GTP or ATP were compared and analyzed, providing new insights into the enormous diversity of biological function of G proteins.
PLANT SIGNALING & BEHAVIOR
(2022)
Review
Pharmacology & Pharmacy
David J. Marcus, Michael R. Bruchas
Summary: Despite the fact that G protein-coupled receptors (GPCRs) are targeted by about 40% of FDA-approved drugs, there is still a lack of understanding of their physiological and functional roles at the systems level. Classic pharmacological experiments and in vitro assays have provided insights into GPCR signaling cascades, but the interaction of these cascades across different cell types, tissues, and organ systems remains unclear. The development of optical tools has allowed researchers to investigate GPCR signaling in vivo and in vitro, providing temporal and spatial resolution. These tools have been used to explore the functional roles of different populations of GPCRs and their signaling cascades at the systems level.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Hannes Schihada, Rawan Shekhani, Gunnar Schulte
Summary: The research team developed and validated eight G protein sensors that can measure the activity of all major families of G proteins, along with a protocol to identify constitutive GPCR or G protein signaling in live cells.
Article
Cell Biology
Mao Zhang, Cheng Zhu, Yuanyuan Duan, Tongbao Liu, Haoping Liu, Chang Su, Yang Lu
Summary: A unique group of PP2C phosphatases from fungi and plants have been found to sense CO2, but not HCO3-, to control diverse cellular programmes. They have intrinsically disordered regions (IDR) that form reversible liquid-like droplets through phase separation and are activated in response to elevated environmental CO2 in an IDR-dependent manner.
NATURE CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Donghoon Ahn, Davide Provasi, Nguyen Minh Duc, Jun Xu, Leslie Salas-Estrada, Aleksandar Spasic, Min Woo Yun, Juyeong Kang, Dongmin Gim, Jaecheol Lee, Yang Du, Marta Filizola, Ka Young Chung
Summary: In this study, a novel Bayesian integrative modeling framework was used to investigate the conformational changes of the beta(2)-adrenergic receptor (β(2)AR)-Gs complex after GDP release and GTP binding. The results showed rapid GTP binding and dissociation of Gas from β(2)AR and G(βγ), and a slow closing of the G(alpha s)α-helical domain. Additionally, the screening identified MAGE D2 as a novel AHD-binding protein that can accelerate the GTP-induced closing of G(alpha s) AHD.
Article
Anesthesiology
Guido Michels, Johann Bauersachs, Bernd W. Boettiger, Hans-Joerg Busch, Burkhard Dirks, Norbert Frey, Carsten Lott, Nadine Rott, Wolfgang Schoels, P. Christian Schulze, Holger Thiele
Summary: This article summarizes and comments on the revised recommendations on basic measures, advanced resuscitation measures, and post-resuscitation treatment in adults in the European guidelines on cardiopulmonary resuscitation.
Article
Biochemistry & Molecular Biology
Greta Verena Freundt, Friedrich Alexander von Samson-Himmelstjerna, Jan-Thorge Nitz, Mark Luedde, Johannes Waltenberger, Thomas Wieland, Norbert Frey, Michael Preusch, Hans-Joerg Hippe
Summary: The study reveals that GPRC5B is upregulated in response to high glucose and vascular inflammation, modulating inflammatory activity and potentially contributing to a positive feedback loop in atherogenesis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cardiac & Cardiovascular Systems
Martin J. Volz, Isabel Hoerbrand, Mathias H. Konstandin, Derliz Mereles, Celine Weiss, Gregor Warnecke, Norbert Frey, Matthias Aurich, Philip W. Raake
Summary: In a single-center retrospective analysis, direct tricuspid valve leaflet repair using the transcatheter PASCAL Ace implant system was associated with reduced TR severity and improved cardiopulmonary exercise capacity.
Article
Cardiac & Cardiovascular Systems
Guido Michels, Johann Bauersachs, Bernd W. Boettiger, Hans-Joerg Busch, Burkhard Dirks, Norbert Frey, Carsten Lott, Nadine Rott, Wolfgang Schoels, P. Christian Schulze, Holger Thiele
Summary: This article summarizes and comments on the revised recommendations of the European guidelines on cardiopulmonary resuscitation, including basic measures and advanced resuscitation measures in adults as well as postresuscitation treatment. The new guidelines integrate the topics of epidemiology and life-saving systems and formulate practical key statements for each chapter.
Article
Cardiac & Cardiovascular Systems
Fabian Linden, Norbert Frey, Christian Erbel
Summary: Polyvascular disease refers to relevant atherosclerosis in two or more vascular regions, with a higher risk of cardiovascular events and mortality, requiring intensive prevention measures.
AKTUELLE KARDIOLOGIE
(2022)
Article
Cardiac & Cardiovascular Systems
Janek Salatzki, Evangelos Giannitsis, Anastasia Hegenbarth, Matthias Mueller-Hennessen, Florian Andre, Hugo A. Katus, Norbert Frey, Moritz Biener
Summary: This study validates the correlation between high-sensitivity cardiac Troponin T (hs-cTnT) values at different time points and contrast-enhanced magnetic resonance imaging (CE-MRI) infarct mass in patients with acute myocardial infarction (AMI). The results demonstrate that hs-cTnT values on admission have a superior correlation with CE-MRI infarct mass.
EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE
(2022)
Review
Cardiac & Cardiovascular Systems
Amr Abdin, Johann Bauersachs, Samira Soltani, Matthias Eden, Norbert Frey, Michael Boehm
Summary: Heart failure remains a global healthcare challenge despite significant developments in pharmacotherapies. There are concerns regarding low medication dosages and incomplete drug classes in real-world settings, and current guidelines lack detailed recommendations. A practical approach algorithm is proposed to assist physicians in treating HF patients.
Article
Pharmacology & Pharmacy
Panagiotis Xynogalos, Ann-Kathrin Rahm, Sebastian Fried, Safak Chasan, Daniel Scherer, Claudia Seyler, Hugo A. Katus, Norbert Frey, Edgar Zitron
Summary: This study analyzed the effect of the antiarrhythmic drug verapamil on the inwardly rectifying potassium current of cardiomyocytes. The results showed that verapamil inhibited the Kir2.1, Kir2.2, and Kir2.3 channels, with the inhibition of Kir2.3 being a previously unknown finding. Further experiments revealed that the inhibition of Kir2.3 by verapamil was dependent on specific binding sites and interference with PIP2 activation. This finding provides a potential target for the development of selective antiarrhythmic drugs targeting Kir2.3 channels.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Veronika Leiss, Roland P. Piekorz, Salvador Castaneda Vega, Christoph Jacoby, Ulrich Floegel, Katja Pexa, Juergen Schrader, Bernd J. Pichler, Sandra Beer-Hammer, Bernd Nuernberg
Summary: This article presents raw and processed data related to the research conducted by Vega et al. (2022). The dataset provides additional insights into the experimental validation of a common carotid artery occlusion (CCAO) model with pretreatment of pertussis toxin (PTX). The data demonstrate the impact of different PTX concentrations on neurological severity measured by Bederson score following CCAO. Furthermore, the data indicate the protective effect of isoflurane on cerebral infarction and neurological deficits, as well as the consequences of PTX pretreatment on reperfusion after occlusion using time-of-flight magnetic resonance angiography.
Article
Biochemistry & Molecular Biology
Mehul V. Makwana, Cleide dos Santos Souza, Barry T. Pickup, Mark J. Thompson, Santosh K. Lomada, Yuxi Feng, Thomas Wieland, Richard F. W. Jackson, Richmond Muimo
Summary: Nonhydrolysable stable analogues of & tau;-phosphohistidine and & pi;-phosphohistidine were designed, synthesized, and used as haptens to generate pHis polyclonal antibodies. The selectivity of the pHis antibodies was assessed by competitive ELISA, and it was found that antibodies generated using phosphopyrazole 8 were selective for & tau;-pHis, while antibodies generated using pyridyl amino amide 13 were selective for & pi;-pHis. Both & tau;- and & pi;-pHis antibodies showed effectiveness in various immunological experiments.
Article
Pharmacology & Pharmacy
Nan Ma, Yohanes Cakrapradipta Wibowo, Phillip Wirtz, Doris Baltus, Thomas Wieland, Sepp Jansen
Summary: Tankyrase inhibitors have an impact on endothelial cell function by altering junctional dynamics, permeability, and migration. Mechanistically, tankyrase inhibition stabilizes angiomotin-like proteins 1 and 2, leading to the suppression of YAP1/TAZ nuclear translocation and TEAD-mediated transcription. Additionally, tankyrase inhibitors disrupt adherens junctions through RhoA-ROCK-mediated F-actin bundling. The actin cytoskeleton plays a role in the regulation of YAP1 and TAZ in endothelial cells.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Yixin Wang, Rachana Eshwaran, Susanne C. Beck, Thomas Wieland, Yuxi Feng
Summary: Diabetic retinopathy (DR) is a common complication of diabetes, and the mechanisms underlying its development are not fully understood. The breakdown of the neurovascular unit (NVU), which involves damage to vascular cells, activation of glial cells, and neuronal dysfunction, plays a crucial role in DR. The activation of the hexosamine biosynthesis pathway (HBP) and increased protein OGlcNAcylation have been identified as key factors in the initiation of DR.
MOLECULAR METABOLISM
(2023)
Article
Cell Biology
Magdolna K. Levay, Lena Throm, Nabil Bahrami, Thomas Wieland
Summary: The stimulation of M2R induces the binding of p190RhoGAP to RGS3L in cardiac myocytes, leading to a change in substrate preference from RhoA to Rac1. This process is mediated by the production of NO through eNOS activation in caveolae. These findings demonstrate the importance of M2R-induced NO production in regulating RhoA activation in cardiac myocytes.
Article
Multidisciplinary Sciences
Sandro Trova, Fei Lin, Santosh Lomada, Matthew Fenton, Bhavini Chauhan, Alexandra Adams, Avani Puri, Alessandro Di Maio, Thomas Wieland, Daniel P. Sewell, Kirstin Dick, Daniel T. Wiseman, Deepti L. Wilks, Margaret M. Goodall, Mark Drayson, Farhat Khanim, Christopher Bunce
Summary: A history of infection is associated with increased risk of AML and MDS. IgM and IgG antibodies against pathogen NDPKs are found in the blood of AML patients, indicating in vivo exposure to NDPKs. Pathogen NDPKs can mimic the pro-survival activity of NM23-H1 and activate NLRP3-inflammasome in monocytes, suggesting their role in the pathogenesis of AML and MDS.
Article
Biochemistry & Molecular Biology
Yixin Wang, Mahmoud Halawa, Anupriya Chatterjee, Rachana Eshwaran, Yi Qiu, Yohanes Cakrapradipta Wibowo, Jianyuan Pan, Thomas Wieland, Yuxi Feng
Summary: This study reveals that a reduction in Cav-1 content in the retina impairs the neurovascular unit, leading to vascular leakage and decreased levels of VEGFR2 and VE-Cadherin in endothelial cells.
MOLECULAR MEDICINE
(2023)