Review
Cell Biology
Federica Liccardo, Alberto Luini, Rosaria Di Martino
Summary: G-protein-coupled receptors (GPCRs) and G-proteins play important roles in various physiological and pathological processes, and can elicit intracellular responses through different signaling pathways. Recent research suggests that they may not only exist on the plasma membrane, but also on endomembranes, initiating or propagating signaling pathways through these organelles. However, further investigation is needed to understand how these alternative intracellular signaling pathways of GPCRs and G-proteins impact the physiological and pathological function of endomembranes.
Review
Biochemistry & Molecular Biology
Kunyou Park, Sungeun Ju, Nari Kim, Seung-Yeol Park
Summary: The Golgi complex is crucial for protein secretion as it regulates cargo sorting and trafficking. Research efforts have focused on understanding the unique stack structure of the Golgi apparatus to unravel the mechanisms of protein secretion through this organelle. Recent insights have also shed light on the signaling pathways controlled by the Golgi complex and their physiological significance.
Article
Cell Biology
Heather E. McFarlane, Daniela Mutwil-Anderwald, Jana Verbancic, Kelsey L. Picard, Timothy E. Gookin, Anja Froehlich, David Chakravorty, Luisa M. Trindade, Jose M. Alonso, Sarah M. Assmann, Staffan Persson
Summary: The study investigated the importance of a family of proteins containing seven transmembrane domains in cellulose synthesis during cell wall integrity stress, revealing their interaction with G protein signaling pathway and their role in regulating CESA trafficking, impacting the response to cell wall integrity stress.
DEVELOPMENTAL CELL
(2021)
Review
Pharmacology & Pharmacy
Rina Pokhrel, Alexandra L. Morgan, Harley R. Robinson, Martin J. Stone, Simon R. Foster
Summary: G protein-coupled receptor (GPCR) activation triggers complex intracellular signalling networks, which have important implications for receptor biology and drug discovery. Phosphoproteomics has emerged as a powerful tool for investigating these networks and accelerating the discovery of new therapeutic targets.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biology
Xihua Yue, Yi Qian, Lianhui Zhu, Bopil Gim, Mengjing Bao, Jie Jia, Shuaiyang Jing, Yijing Wang, Chuanting Tan, Francesca Bottanelli, Pascal Ziltener, Sunkyu Choi, Piliang Hao, Intaek Lee
Summary: ACBD3 may regulate KDEL receptor trafficking by modulating Arf1-dependent tubule formation. Depletion of ACBD3 leads to re-localization of KDEL receptor to the ER through accelerated retrograde trafficking. This is caused by altering KDEL receptor interaction with Protein Kinase A and Arf1/ArfGAP1, resulting in increased Arf1-GTP-dependent tubular carrier formation at the Golgi.
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
Cell Biology
Chuanting Tan, Yulei Du, Lianhui Zhu, Shuaiyang Jing, Jingkai Gao, Yi Qian, Xihua Yue, Intaek Lee
Summary: KDEL receptor-1 regulates homeostasis in the early secretory pathway by capturing and retrieving ER chaperones. Our study demonstrates that ACBD3 and Rab4A are essential for the trafficking of KDEL receptor from the Golgi to the plasma membrane, independent of PKA- and Src kinase-mediated mechanisms.
Review
Biochemistry & Molecular Biology
Yulong Ren, Yongfei Wang, Yu Zhang, Tian Pan, Erchao Duan, Xiuhao Bao, Jianping Zhu, Xuan Teng, Pengcheng Zhang, Chuanwei Gu, Hui Dong, Fan Wang, Yunlong Wang, Yiqun Bao, Yihua Wang, Jianmin Wan
Summary: Seed storage proteins (SSPs) are the major protein nutrition sources for human and livestock, and they are transported through a plant-specific endomembrane system. Recent studies have uncovered the complex network controlling SSP trafficking, involving both evolutionarily conserved molecular machineries and plant-unique regulators. This review summarizes the current knowledge of protein body biogenesis and endomembrane-mediated SSP transport, and discusses cutting-edge strategies for advancing the field.
Article
Plant Sciences
Deepanksha Arora, Daniel Van Damme
Summary: Endomembrane trafficking allows proteins and lipids to flow between different endomembrane compartments in eukaryotic cells, largely through vesicle-mediated transport. This process involves packaging transmembrane proteins into vesicles, followed by vesicle scission, uncoating, and fusion at the target membrane. Three major trafficking pathways (anterograde, retrograde, endocytic) operate inside cells, each involving specific machinery and coat proteins for packaging and delivery along the pathways.
Article
Chemistry, Multidisciplinary
Hsin-Yung Yen, Idlir Liko, Wanling Song, Parth Kapoor, Fernando Almeida, Joanna Toporowska, Karolina Gherbi, Jonathan T. S. Hopper, Steven J. Charlton, Argyris Politis, Mark S. P. Sansom, Ali Jazayeri, Carol Robinson
Summary: This study presents a mass spectrometry-based approach to investigate the biased signaling and allosteric modulation of the beta(1)-adrenergic receptor in response to different ligands. The researchers discovered that isoprenaline can act as a biased agonist and that endogenous zinc ions enhance the binding between the receptor and G(s) proteins.
Review
Cell Biology
F. C. Palazzo, R. Sitia, T. Tempio
Summary: In multicellular organisms, cells communicate through cognate interactions between membrane and secretory proteins. The folding of these proteins is assisted by chaperones and enzymes in the early secretory compartment (ESC), preventing their transport beyond the Golgi. Cells can selectively secrete certain ESC residents through differential intracellular distribution and release mechanisms.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Estefania Y. Ojeda-Muniz, Brenda Rodriguez-Hernandez, Kerlys G. Correoso-Brana, Petra L. Segura-Landa, Antony A. Boucard
Summary: Adhesion G protein-coupled receptors (aGPCRs) possess a unique topology with a GPCR proteolysis site (GPS) that generates functionally distinct fragments upon autoproteolysis. The function of GPS cleavage has been enigmatic, but this study reveals that cleavage deficiency leads to biased signalling in aGPCRs. Specifically, cleavage-deficient ADGRL3 exhibits constitutive activity and shows a signalling bias towards select G proteins.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Multidisciplinary Sciences
Arne Thies, Vikram Sunkara, Sourav Ray, Hanna Wulkow, M. Oezguer Celik, Fatih Yergoez, Christof Schuette, Christoph Stein, Marcus Weber, Stefanie Winkelmann
Summary: We have successfully designed, synthesized, and tested the prototype opioid painkiller NFEPP, which does not have adverse side effects. The design process was based on mathematical modeling of interactions between G-protein coupled receptors (GPCRs) and ligands, considering the different functions of GPCRs under pathological and healthy conditions. Additionally, we have proposed a novel stochastic model of GPCR function that takes into account intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels, which depend on the parameters of inflamed and healthy tissue (pH, radicals). The model has been validated using in vitro experimental data for NFEPP and fentanyl at different pH values and radical concentrations.
SCIENTIFIC REPORTS
(2023)
Review
Cell Biology
Haoran Jiang, Daniella Galtes, Jialu Wang, Howard A. Rockman
Summary: This review explores the signaling pathways, dynamic structures, and physiological relevance of the three most important GPCR signaling effectors in the cardiovascular system: heterotrimeric G proteins, GPCR kinases (GRKs), and 8-arrestins. It summarizes their prominent roles in GPCR pharmacology before transitioning into less well-explored areas. The application of new technologies has contributed to an increasing understanding of GPCR structure and downstream effectors.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Ida Romano, Giuseppe Granata, Annarita Poli, Ilaria Finore, Edoardo Napoli, Corrada Geraci
INTERNATIONAL BIODETERIORATION & BIODEGRADATION
(2020)
Editorial Material
Immunology
Carl F. Nathan, Michel C. Nussenzweig, Teodoro Pulvirenti
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Review
Oncology
Carmen Ruggiero, Enzo Lalli
Summary: Cancer is characterized by a loss or perturbation of typical cell behaviors. Dysregulation of the cytoskeleton contributes to cancer progression, with metastasis accounting for 90% of deaths from solid tumors. Targeting the cytoskeleton emerges as an effective approach for developing anti-metastatic drugs.
CANCER AND METASTASIS REVIEWS
(2021)
Article
Infectious Diseases
Magdalena Kapustova, Giuseppe Granata, Edoardo Napoli, Andrea Puskarova, Maria Buckova, Domenico Pangallo, Corrada Geraci
Summary: Nanotechnology, specifically nanoencapsulation of plant essential oils with antifungal activity, shows promise in overcoming resistance in fungal species. The essential oil nanosystems exhibited lower MIC and MFC values compared to pure essential oils, indicating their potential as ecofriendly alternatives to synthetic products.
Article
Pharmacology & Pharmacy
Magdalena Kapustova, Andrea Puskarova, Maria Buckova, Giuseppe Granata, Edoardo Napoli, Adriana Annusova, Monika Mesarosova, Katarina Kozics, Domenico Pangallo, Corrada Geraci
Summary: This study demonstrates the effectiveness of poly(epsilon-caprolactone) nanocapsules loaded with thyme and oregano essential oils in reducing microbial and biofilm growth without cytotoxicity on human keratinocyte cells, as well as the absence of DNA damage induction.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Editorial Material
Pharmacology & Pharmacy
Carmen Ruggiero, Mabrouka Doghman-Bouguerra, Enzo Lalli
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Francesca Potenza, Maria Concetta Cufaro, Linda Di Biase, Valeria Panella, Antonella Di Campli, Anna Giulia Ruggieri, Beatrice Dufrusine, Elena Restelli, Laura Pietrangelo, Feliciano Protasi, Damiana Pieragostino, Vincenzo De Laurenzi, Luca Federici, Roberto Chiesa, Michele Sallese
Summary: Marinesco-Sjogren syndrome is a rare multisystem pediatric disorder caused by mutations in the SIL1 gene, resulting in endoplasmic reticulum folding abnormalities. Research on skin fibroblasts from patients revealed metabolic changes and UPR activation despite no overt effects on cell morphology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Letter
Oncology
Carmen Ruggiero, Barbara Altieri, Edith Arnold, Lourdes Siqueiros-Marquez, Mabrouka Doghman-Bouguerra, Mario Detomas, Nelly Durand, Marielle Jarjat, Max Kurlbaum, Fabrice Chatonnet, Timo Deutschbein, Carmen Clapp, Enzo Lalli
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Cell Biology
Verena Damiani, Maria Concetta Cufaro, Maurine Fucito, Beatrice Dufrusine, Claudia Rossi, Piero Del Boccio, Luca Federici, Maria Caterina Turco, Michele Sallese, Damiana Pieragostino, Vincenzo De Laurenzi
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer mortality worldwide. This study investigated the crosstalk between PDAC cells and associated fibroblasts. Proteomic analysis was used to identify proteins released from PDAC cells and detect proteostatic changes in normal fibroblasts treated with PDAC conditioned medium. The results suggest that the activation of migration, vasculogenesis, cellular homeostasis, metabolism of amino acids, and reduced apoptosis may be regulated by ITGB3 and TGFB1/2 followed by SMAD3, STAT3, and BAG3 activation.
Article
Pharmacology & Pharmacy
Giuseppe Granata, Carla Riccobene, Edoardo Napoli, Corrada Geraci
Summary: Plant essential oils have limited direct use in pharmaceutical applications due to their volatility, stability issues, and low toxicity. However, nanoencapsulation can overcome these limitations by improving bioaccessibility and bioavailability. In this study, nanocapsules containing Foeniculum vulgare Mill. essential oil were successfully prepared using a preformed polymer method. The nanocapsules exhibited good stability and high encapsulation efficiency, making them suitable for potential applications in the pharmaceutical and nutraceutical sectors.
Review
Biochemistry & Molecular Biology
Ilaria Cela, Beatrice Dufrusine, Claudia Rossi, Alberto Luini, Vincenzo De Laurenzi, Luca Federici, Michele Sallese
Summary: KDELRs are ubiquitous receptors involved in cell quality control and stress responses. Mutations in KDELRs are associated with various diseases, making them potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Ilaria Cela, Maria Concetta Cufaro, Maurine Fucito, Damiana Pieragostino, Paola Lanuti, Michele Sallese, Piero Del Boccio, Adele Di Matteo, Nerino Allocati, Vincenzo De Laurenzi, Luca Federici
Summary: The role of nucleostemin in acute myeloid leukemia (AML) is unclear. Using a proteomics approach, researchers found that silencing nucleostemin in AML cells had effects on DNA repair and increased DNA damage rates, indicating its potential importance in AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Michele Sallese, Konstantinos Efthymakis, Michele Marchioni, Benedetto Neri, Beatrice Dufrusine, Enrico Dainese, Marta Di Nicola, Matteo Neri
Summary: Coeliac disease (CeD) is an immune-mediated disorder triggered by gluten, involving autoimmune damage to the intestines and other systems. The Th1 inflammatory response and innate immune response play important roles in its pathogenesis. Gene expression analysis found key cytokines and immune pathways involved. Comparison with non-celiac gluten sensitivity (NCGS) revealed molecular overlap, suggesting a common root (dysregulated long non-coding RNAs) for these diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Giuseppe Granata, Stefano Stracquadanio, Marco Leonardi, Edoardo Napoli, Graziella Malandrino, Viviana Cafiso, Stefania Stefani, Corrada Geraci
Summary: The study reports the preparation and physicochemical characterization of chitosan nanoparticles loaded with Thymus capitatus and Origanum vulgare essential oils, which demonstrate enhanced bactericidal activity against foodborne pathogens. These ecofriendly nanosystems could serve as a promising alternative to synthetic preservatives for health and food safety.
Article
Pharmacology & Pharmacy
Debora Santonocito, Giuseppe Granata, Corrada Geraci, Annamaria Panico, Edy Angela Siciliano, Giuseppina Raciti, Carmelo Puglia