Article
Chemistry, Multidisciplinary
Mohammad Javad Afshari, Cang Li, Jianfeng Zeng, Jiabin Cui, Shuwang Wu, Mingyuan Gao
Summary: This study reports a biocompatible, self-illuminating probe with second near-infrared emission for improving the cytotoxicity concerns, penetration depth, and spatiotemporal resolution of bioluminescence imaging. It has been successfully applied for in vivo tumor imaging in mice.
Article
Chemistry, Multidisciplinary
Brittany R. Benlian, Pavel E. Z. Klier, Kayli N. Martinez, Marie K. Schwinn, Thomas A. Kirkland, Evan W. Miller
Summary: Q-BOLT is a small-molecule enzyme pair for optical voltage sensing that utilizes quenching of bioluminescence to visualize changes in membrane potential in live cells. It combines three distinct readouts - QRET, BRET, and the ratio between bioluminescence emission and BRET - to accurately report membrane potential oscillations in HEK 293T cells and hiPSCs, without the need for excitation light.
Article
Biochemistry & Molecular Biology
Hahoon Hong, Byoungsu Yoon, Sungho Ghil
Summary: Lysophosphatidylinositol (LPI) and sphingosine-1-phosphate (S1P) are bioactive lipids that play important roles in cellular events such as proliferation, migration, and cancer progression. They act as ligands for G-protein coupled GPR55 and S1P receptors, respectively, and activate specific signaling pathways. Interestingly, the study found that co-activation of GPR55 and S1P receptors inhibits their stimulatory effects on colon cancer progression.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sung-Bae Kim, Ryo Nishihara, Ramasamy Paulmurugan
Summary: We identified the best resonance energy donor for near infrared bioluminescence resonance energy transfer (NIR-BRET) templates and achieved high sensitivity in monitoring molecular events in cells. The established templates, fused with fluorescent proteins, showed a large blue-to-red shift and were used in new NIR-BRET systems for imaging steroid hormone activities. The NIR-BRET systems demonstrated specific luminescence signals upon exposure to different steroid hormones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Virology
Andrea Happle, Holger Jeske, Tatjana Kleinow
Summary: The study reveals that the nuclear shuttle protein (NSP) and movement protein (MP) of Abutilon mosaic virus use separate cellular pathways for viral DNA transport in plants, without physical interaction between the two proteins.
Review
Endocrinology & Metabolism
Gaoxian Chen, Detlef Obal
Summary: G protein-coupled receptors (GPCRs) are important transmembrane proteins involved in many physiological processes, and their targeted drug development has been widely promoted. However, research findings generated in immortal cell lines have limitations in correlating with clinical patients. Human induced pluripotent stem cells (hiPSCs) have the potential to overcome these limitations and expand GPCR research towards personalized medicine. This review discusses the challenges of detecting GPCRs in hiPSCs and summarizes existing and new labeling methods.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eunju Song, Sungho Ghil
Summary: Cannabinoid receptor 2 (CB2) and lysophosphatidic acid receptor 5 (LPA5) can interact with each other and affect the physiological activities of colon cancer cells, indicating the possibility of physical and functional crosstalk between the two receptors.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Nanoscience & Nanotechnology
Shaohua Qu, Zihan Qiao, Wencheng Zhong, Kangqiang Liang, Xiue Jiang, Li Shang
Summary: This study established a FRET-based platform for monitoring the dynamic evolution of protein corona in complex biological media. The nature of initially adsorbed proteins on quantum dots significantly affects subsequent exchange behavior, with only a limited proportion of proteins being involved in the exchange process, which is also significantly influenced by the surface chirality of the quantum dots.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Review
Chemistry, Multidisciplinary
Yuyan Jiang, Kanyi Pu
Summary: Optical imaging is a crucial tool in clinical diagnostics and biomedical research, with autofluorescence-free molecular probes significantly improving imaging sensitivity and specificity. The Review focuses on the advancements and challenges in developing these probes for in vivo imaging and in vitro biosensors. Future prospects for next-generation autofluorescence-free molecular probes are optimistic.
Review
Plant Sciences
Zhikun Duan, Kaiwen Li, Wenwen Duan, Junli Zhang, Jingjing Xing
Summary: This article highlights the importance of using FRET technology to study interactions of plant membrane proteins, providing an overview of its applications in quantifying dynamic interactions and assemblies, as well as sensors for quantifying signaling molecule homeostasis and kinase activity. The recent applications of advanced FRET sensors in probing membrane protein interactions, stoichiometry, and clustering have shed light on the complex biological functions of membrane proteins in living plant cells.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Chemistry, Multidisciplinary
Ying Xiong, Yiyu Zhang, Zefan Li, Md Shamim Reza, Xinyu Li, Xiaodong Tian, Hui-wang Ai
Summary: The NanoLuc luciferase and its furimazine substrate have greatly improved bioluminescence assays and imaging. However, their use for mammalian tissue imaging is limited by the low tissue penetration of blue photons. In this study, a mutant NLuc called QLuc was developed, which catalyzes the oxidation of a synthetic QTZ luciferin to produce bright and red-shifted emission. This red-shifted luciferase showed improved performance for imaging deep-tissue targets in live mice. Using QLuc, the researchers also demonstrated the use of immunoBLI for molecular imaging of tumor-associated antigens in a xenograft mouse model. QLuc is expected to have broad applications in noninvasive mammalian imaging, and immunoBLI serves as a convenient and nonradioactive molecular imaging tool for animal models in basic and preclinical research.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Eva Wisniewski, Domonkos Czaran, Fanni Kovacs, Eniko Bahurek, Afrodite Nemeth, Peter Sasvari, Gergo Szanda, Aladar Pettko-Szandtner, Eva Klement, Erzsebet Ligeti, Roland Csepanyi-Komi
Summary: This study reveals the regulatory role of different phosphorylation patterns on the GAP activity, superoxide production, and phagocytic effect of ARHGAP25.
Review
Biochemistry & Molecular Biology
Duc Loc Sai, Jieun Lee, Duc Long Nguyen, Young-Pil Kim
Summary: Photodynamic therapy (PDT) utilizes photosensitive drugs that generate reactive oxygen species when exposed to light, killing cancer cells. Recent advancements in protein-based photosensitive drugs, nanomaterials, and luminescence are improving the effectiveness of PDT. Researchers are focusing on developing strategies to enhance tumor treatment outcomes and address challenges such as drug side effects and light delivery.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Chemistry, Multidisciplinary
Lan Mi, Qikun Yu, Aruni P. K. K. Karunanayake Mudiyanselage, Rigumula Wu, Zhining Sun, Ru Zheng, Kewei Ren, Mingxu You
Summary: RNA-based nanostructures and molecular devices have been widely used for biosensors and genetic regulators. However, the high reliance on fluorescence as the readout can cause issues such as high background and phototoxicity. In this study, we developed the first genetically encoded RNA-based bioluminescence resonance energy transfer (BRET) sensors for real-time target detection in living cells. This novel system has potential applications in bioanalysis and nanomedicine for engineering biosensors, characterizing cellular RNA-protein interactions, and high-throughput screening or in vivo imaging.
Article
Chemistry, Analytical
Mengdi Li, Xiangyi Huang, Jicun Ren
Summary: The study introduces a highly efficient CRET-Pdots system for in vivo imaging and photodynamic therapy, featuring intense multicolor CL, adjustable emission wavelength, and high CRET efficiency. These CRET-Pdots are sensitive to ROS, possess excellent biocompatibility and catalytic activity.
ANALYTICAL CHEMISTRY
(2021)
Article
Cell Biology
Bas Brouwers, Edson Mendes de Oliveira, Maria Marti-Solano, Fabiola B. F. Monteiro, Suli-Anne Laurin, Julia M. Keogh, Elana Henning, Rebecca Bounds, Carole A. Daly, Shane Houston, Vikram Ayinampudi, Natalia Wasiluk, David Clarke, Bianca Plouffe, Michel Bouvier, M. Madan Babu, I. Sadaf Farooqi, Jacek Mokrosinski
Summary: Research on melanocortin-4 receptor (MC4R) mutations associated with obesity reveals the importance of endocytosis, intracellular trafficking, and homodimerization in regulating MC4R function, supporting the development of novel therapies for weight loss.
Letter
Cell Biology
Lu Xu, Bo Chen, Hannes Schihada, Shane C. Wright, Ainoleena Turku, Yiran Wu, Gye-Won Han, Maria Kowalski-Jahn, Pawel Kozielewicz, Carl-Fredrik Bowin, Xianjun Zhang, Chao Li, Michel Bouvier, Gunnar Schulte, Fei Xu
Article
Biochemistry & Molecular Biology
Shane C. Wright, Michel Bouvier
Summary: GPCRs continue to be a focus in drug discovery efforts due to their widespread expression and broad role in signal transduction. Despite over 800 GPCRs sharing a common architecture, unique differences govern ligand specificity and pathway selectivity. Recent biosensor development has reinforced the idea that biased signaling may become mainstream in drug discovery programs.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jenna Giubilaro, Doris A. Schuetz, Tomasz M. Stepniewski, Yoon Namkung, Etienne Khoury, Monica Lara-Marquez, Shirley Campbell, Alexandre Beautrait, Sylvain Armando, Olivier Radresa, Jean Duchaine, Nathalie Lamarche-Vane, Audrey Claing, Jana Selent, Michel Bouvier, Anne Marinier, Stephane A. Laporte
Summary: A novel dual Ras and ARF6 inhibitor named Rasarfin was identified in a high-throughput screen for receptor trafficking inhibitors. Rasarfin blocks agonist-mediated internalization of GPCRs, inhibits ERK1/2 signaling, MAPK and Akt signaling, and prevents cancer cell proliferation. The unique binding modality of Rasarfin within the SOS-binding domain of Ras was revealed through in silico modeling and in vitro studies, indicating its potential for inhibiting oncogenic cellular responses.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Peter Kolb, Terry Kenakin, Stephen P. H. Alexander, Marcel Bermudez, Laura M. Bohn, Christian S. Breinholt, Michel Bouvier, Stephen J. Hill, Evi Kostenis, Kirill A. Martemyanov, Rick R. Neubig, H. Ongun Onaran, Sudarshan Rajagopal, Bryan L. Roth, Jana Selent, Arun K. Shukla, Martha E. Sommer, David E. Gloriam
Summary: GPCRs regulate various physiological processes and their effects depend on the pairing of a receptor and a ligand. Ligands that induce biased signalling can lead to better drug effects and fewer side effects. However, ligand bias is complex, making it necessary to develop guidelines for designing and reporting biased signalling experiments.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Janik B. Hedderich, Margherita Persechino, Katharina Becker, Franziska M. Heydenreich, Torben Gutermuth, Michel Bouvier, Moritz Buenemann, Peter Kolb
Summary: Researchers computationally describe alternative allosteric pockets in G-protein-coupled receptors, identifying nine previously untargeted sites for synthetic ligands. They further investigate the potential of modulating receptor function through ligand binding to these sites.
NATURE COMMUNICATIONS
(2022)
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.
Article
Biology
Charlotte Avet, Arturo Mancini, Billy Breton, Christian Le Gouill, Alexander S. Hauser, Claire Normand, Hiroyuki Kobayashi, Florence Gross, Mireille Hogue, Viktoriya Lukasheva, Stephane St-Onge, Marilyn Carrier, Madeleine Heroux, Sandra Morissette, Eric B. Fauman, Jean-Philippe Fortin, Stephan Schann, Xavier Leroy, David E. Gloriam, Michel Bouvier
Summary: This study presents a set of BRET sensors to monitor the activation of G protein subtypes without modifying the receptors or G proteins. Profiling 100 therapeutically relevant human GPCRs resulted in pathway-specific concentration-response curves, revealing a diversity of coupling profiles.
Article
Genetics & Heredity
Marta Bialic, Baraah Al Ahmad Nachar, Maria Kozlak, Vincent Coulon, Etienne Schwob
Summary: This article describes a simple and robust method to measure the duration of the S phase in cell cultures. It utilizes a dual EdU-BrdU pulse-labeling regimen with incremental thymidine chases and quantification by flow cytometry. The method does not require cell synchronization or genome engineering and can be used for various types of cells.
Article
Pharmacology & Pharmacy
Franziska Marie Heydenreich, Bianca Plouffe, Aurelien Rizk, Dalibor Milic, Joris Zhou, Billy Breton, Christian Le Gouill, Asuka Inoue, Michel Bouvier, Dmitry B. Veprintsev
Summary: By modeling G protein activation as a Michaelis-Menten reaction, we have developed a novel method for quantifying signaling bias. V2R activates, or at least engages, G proteins from all G protein subfamilies, including Gi2, Gz, Gq, G12, and G13. Their relative activation may explain its Gs-independent signaling.
MOLECULAR PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Valeria Burghi, Justine S. Paradis, Adam Officer, Sendi Rafael Adame-Garcia, Xingyu Wu, Edda S. F. Matthees, Benjamin Barsi-Rhyne, Dana J. Ramms, Lauren Clubb, Monica Acosta, Pablo Tamayo, Michel Bouvier, Asuka Inoue, Mark von Zastrow, Carsten Hoffmann, J. Silvio Gutkind
Summary: This study focuses on the role of beta-arrestins in G protein-coupled receptor (GPCR) signaling. It is found that while G proteins are essential for GPCR signaling, beta-arrestins play a more prominent role in signal compartmentalization and modulation of gene expression.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Shane C. Wright, Aikaterini Motso, Stefania Koutsilieri, Christian M. Beusch, Pierre Sabatier, Alessandro Berghella, Elodie Blondel-Tepaz, Kimberley Mangenot, Ioannis Pittarokoilis, Despoina-Christina Sismanoglou, Christian Le Gouill, Jesper V. Olsen, Roman A. Zubarev, Nevin A. Lambert, Alexander S. Hauser, Michel Bouvier, Volker M. Lauschke
Summary: This study investigates the subcellular location of GLP-1R signaling events and reveals associations between signaling profiles and adverse drug reactions, providing important insights for rational drug design and improving the therapeutic potential of GLP-1R agonists.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Ahmed Mansour, Karim Nagi, Paul Dallaire, Viktoriya Lukasheva, Christian Le Gouill, Michel Bouvier, Graciela Pineyro
Summary: Long-term exposure to opioid receptor agonists leads to adaptations in the AC pathway, resulting in enhanced cAMP production and impacting chronic pain management. Different DOPr agonists exhibit distinct signaling profiles, with functional selectivity influenced by Ca2+ mobilization.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Tomasz Maciej Stepniewski, Arturo Mancini, Richard Agren, Mariona Torrens-Fontanals, Meriem Semache, Michel Bouvier, Kristoffer Sahlholm, Billy Breton, Jana Selent
Summary: This research combines various techniques to study the actions of dopamine on the dopaminergic D-2 receptor, revealing how neurotransmitter binding leads to the activation of different effectors. Experiments show that key residues in TM5 and TM6 are involved in coupling with effectors, while sequence variation at position 6.55 can fine-tune beta-arrestin recruitment and regulate receptor signaling and internalization of neurotransmitter receptors.
Article
Chemistry, Medicinal
Max Meyrath, Christie B. Palmer, Nathan Reynders, Alain Vanderplasschen, Markus Ollert, Michel Bouvier, Martyna Szpakowska, Andy Chevigne
Summary: The study compared the activation of ACKR3 by ADM and PAMP, finding that PAMP had a stronger potency towards ACKR3 than ADM. Importantly, PAMP-12 was efficiently internalized by ACKR3 without inducing G protein or ERK signaling in vitro.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)