Article
Pharmacology & Pharmacy
Mark von Zastrow
Summary: Advances in proteomic methodologies based on quantitative mass spectrometry are revolutionizing pharmacology and experimental biology. This review focuses on the interplay between G protein-coupled receptor signaling and trafficking in the endocytic network, highlighting recent progress and challenges in elucidating the cellular basis of drug action using proteomic approaches.
MOLECULAR PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Melissa Girard, Steve Dagenais Bellefeuille, Emilie Eiselt, Guillaume Arguin, Jean-Michel Longpre, Philippe Sarret, Fernand-Pierre Gendron
Summary: This study found that endosomal trafficking plays an important role in G protein-coupled receptor (GPCR) signaling. UDP selectively activates GPCR P2Y6 as a signaling molecule. The study found that MRS2693 and UDP have different effects on the internalization of the P2Y6 receptor, with MRS2693 inducing P2Y6 internalization through an independent caveolin-dependent mechanism. This study provides insights for the development of bias ligands that can influence P2Y6 signaling.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
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)
Review
Cell Biology
Karina A. Pena
Summary: The canonical model for GPCR activation assumes that activation occurs only at the cell surface and is turned off by receptor internalization. However, recent research has shown that some internalized GPCRs can continue to signal from endosomes, which has physiological implications.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Jean-Pierre Vilardaga, Ieva Sutkeviciute, Karina A. Pena
Summary: The study demonstrates the significant impact of localized cAMP production on cellular functions, particularly in phospho-responses, as revealed through phospho-proteomic analysis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Review
Cell Biology
Ping Lyu, Bo Li, Peiran Li, Ruiye Bi, Chen Cui, Zhihe Zhao, Xuedong Zhou, Yi Fan
Summary: This article reviews the effects of PTH, PTHrP, and PTH1R signaling on MSCs in the orofacial region, as well as the potential therapeutic applications for dental and bone regeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Angus Li, Samuel Liu, Rennica Huang, Seungkirl Ahn, Robert J. Lefkowitz
Summary: G protein-coupled receptors (GPCRs) regulate cellular signaling pathways by coupling to G proteins and beta-arrestins. SII, an analog of AngII, activates cellular signaling through beta-arrestin-2-dependent mechanisms but fails to activate G protein. However, overexpression of the receptor can distort the bias of ligands and may not accurately reflect their signaling profile in physiologically relevant contexts.
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.
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.
Article
Multidisciplinary Sciences
Xiuwen Zhai, Chunyou Mao, Qingya Shen, Shaokun Zang, Dan-Dan Shen, Huibing Zhang, Zhaohong Chen, Gang Wang, Changming Zhang, Yan Zhang, Zhihong Liu
Summary: In this study, the cryo-electron microscopy structures of PTH- and ABL-bound PTH1R-Gs complexes were reported, revealing the molecular basis of ligand duration. The results provide insights into the mechanistic understanding of ligand-mediated prolonged or transient signaling.
NATURE COMMUNICATIONS
(2022)
Review
Immunology
Yi Wang, Cheng-long Zhu, Peng Li, Qiang Liu, Hui-ru Li, Chang-meng Yu, Xiao-ming Deng, Jia-feng Wang
Summary: Sepsis is a life-threatening dysfunction caused by an uncontrolled host response to infection, leading to respiratory dysfunction and acute respiratory distress syndrome (ARDS). Neutrophils, the first line of defense against infection, play a major role in sepsis. However, studies have shown that despite high levels of chemokines at the site of infection, neutrophils cannot migrate properly and instead accumulate in the lungs, causing tissue damage and ARDS. Dysregulation of chemokine receptors, particularly G protein-coupled receptors (GPCRs), is implicated in impaired neutrophil migration. This review summarizes the signaling pathways and mechanisms by which GPCR dysfunction in sepsis leads to impaired neutrophil chemotaxis and proposes potential targets for intervention to improve neutrophil chemotaxis.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Endocrinology & Metabolism
Davide Calebiro
Summary: GPCRs, the largest family of membrane receptors, play a crucial role in the endocrine system and are associated with various diseases. By using innovative optical methods to study GPCR signaling, researchers have unraveled long-debated questions about GPCR signaling mechanisms and their connection to human diseases, potentially paving the way for novel therapeutic approaches for diseases.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Siyuan Shen, Chang Zhao, Chao Wu, Suyue Sun, Ziyan Li, Wei Yan, Zhenhua Shao
Summary: GPCRs, as the largest family of transmembrane proteins, regulate various physiological processes. However, their complicated signal transduction pathways and difficulties in drug development have presented challenges. By identifying new ligands that bind to allosteric sites, safer drugs for treating various diseases can be designed.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Preethi C. Karnam, Sergey A. Vishnivetskiy, Vsevolod V. Gurevich
Summary: Arrestins are a small family of proteins that bind G protein-coupled receptors (GPCRs) with high affinity to active phosphorylated GPCRs. They must have two sensors, which detect receptor-attached phosphates and the active receptor conformation independently, enabling transition into a high-affinity receptor-binding state. This transition involves a global conformational rearrangement that stabilizes the complex by bringing additional elements of the arrestin molecule in contact with a GPCR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Vincent B. Luscombe, Luis Alberto Baena-Lopez, Carole J. R. Bataille, Angela J. Russell, David R. Greaves
Summary: In this study, heterologous cell lines with low GPR84 expression levels were developed to mimic the response of primary cells in a label-free cell electrical impedance sensing system. It was found that DL-175 exhibited a delayed impedance response, a delayed and suppressed activation of Akt, and impaired ability to internalise GPR84 from the plasma membrane compared to 6-OAU. These signalling differences were transient and occurred only at early time points in the low expressing cell lines, highlighting the importance of receptor number and kinetic readouts when evaluating signalling bias. These findings provide new insights into GPR84 signalling and the evaluation of newly developed agonists.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Urology & Nephrology
Yaoxian Xu, Andrew J. Streets, Andrea M. Hounslow, Uyen Tran, Frederic Jean-Alphonse, Andrew J. Needham, Jean-Pierre Vilardaga, Oliver Wessely, Michael P. Williamson, Albert C. M. Ong
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2016)
Review
Endocrinology & Metabolism
Ross W. Cheloha, Samuel H. Gellman, Jean-Pierre Vilardaga, Thomas J. Gardella
NATURE REVIEWS ENDOCRINOLOGY
(2015)
Article
Biochemistry & Molecular Biology
Jennifer C. McGarvey, Kunhong Xiao, Shanna L. Bowman, Tatyana Mamonova, Qiangmin Zhang, Alessandro Bisello, W. Bruce Sneddon, Juan A. Ardura, Frederic Jean-Alphonse, Jean-Pierre Vilardaga, Manojkumar A. Puthenveedu, Peter A. Friedman
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Candice G. T. Tahimic, Roger K. Long, Takuo Kubota, Maggie Yige Sun, Hashem Elalieh, Chak Fong, Alicia T. Menendez, Yongmei Wang, Jean-Pierre Vilardaga, Daniel D. Bikle
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Frederic G. Jean-Alphonse, Vanessa L. Wehbi, Jingming Chen, Masaki Noda, Juan M. Taboas, Kunhong Xiao, Jean-Pierre Vilardaga
NATURE CHEMICAL BIOLOGY
(2017)
Letter
Multidisciplinary Sciences
Yalikun Suofu, Diane L. Carlisle, Jean-Pierre Vilardaga, Robert M. Friedlander
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Biochemistry & Molecular Biology
Nyla Naim, Alex D. White, Jeff M. Reece, Mamta Wankhede, Xuefeng Zhang, Jean-Pierre Vilardaga, Daniel L. Altschuler
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Chemistry, Multidisciplinary
Shi Liu, Frederic G. Jean-Alphonse, Alex D. White, Denise Wootten, Patrick M. Sexton, Thomas J. Gardella, Jean-Pierre Vilardaga, Samuel H. Gellman
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Review
Endocrinology & Metabolism
Ieva Sutkeviciute, Lisa J. Clark, Alex D. White, Thomas J. Gardella, Jean-Pierre Vilardaga
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2019)
Review
Biochemistry & Molecular Biology
Ieva Sutkeviciute, Jean-Pierre Vilardaga
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Editorial Material
Biochemistry & Molecular Biology
Jean-Pierre Vilardaga, Ieva Sutkeviciute, Karina A. Pena
Summary: The study demonstrates the significant impact of localized cAMP production on cellular functions, particularly in phospho-responses, as revealed through phospho-proteomic analysis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Karina A. Pena, Alex D. White, Sofya Savransky, Ignacio Portales Castillo, Frederic G. Jean-Alphonse, Thomas J. Gardella, Ieva Sutkeviciute, Jean-Pierre Vilardaga
Summary: This study investigates the signaling pathway and biased signaling properties of native PTHrP protein hormone acting with PTHR. Using fluorescence imaging approaches, the study demonstrates that PTHrP(1-141) displays biased agonist signaling properties that are not mimicked by PTHrP1-36. The molecular basis for this biased signaling difference is attributed to the stabilization of a singular PTHR conformation and PTHrP(1-141) sensitivity to heparin.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Endocrinology & Metabolism
Jean-Pierre Vilardaga, Lisa J. Clark, Alex D. White, Ieva Sutkeviciute, Ji Young Lee, Ivet Bahar
Summary: The classical paradigm of G protein-coupled receptor signaling is being revised as several receptors have been found to engage in sustained signaling responses from subcellular compartments. PTH1R, an important GPCR for calcium and phosphate regulation, can mediate different modes of cAMP signaling. Recent studies have uncovered the structural and signaling mechanisms of PTH1R and its potential pharmacological outputs. Understanding the spatial and temporal aspects of PTH1R signaling is important for drug development targeting metabolic bone and mineral diseases.
Article
Biology
Ignacio Portales-Castillo, Thomas Dean, Ross W. Cheloha, Brendan A. Creemer, Jean-Pierre Vilardaga, Sofya Savransky, Ashok Khatri, Harald Juppner, Thomas J. Gardella
Summary: Three mutations in the PTH1R gene have been identified in patients with Eiken syndrome, resulting in altered cAMP signaling and impaired recruitment of beta-arrestin2. These findings highlight the critical role of PTH1R-beta-arrestin interaction in regulating bone formation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Li-Hua Zhao, Shanshan Ma, Ieva Sutkeviciute, Dan-Dan Shen, X. Edward Zhou, Parker W. de Waal, Chen-Yao Li, Yanyong Kang, Lisa J. Clark, Frederic G. Jean-Alphonse, Alex D. White, Dehua Yang, Antao Dai, Xiaoqing Cai, Jian Chen, Cong Li, Yi Jiang, Tomoyuki Watanabe, Thomas J. Gardella, Karsten Melcher, Ming-Wei Wang, Jean-Pierre Vilardaga, H. Eric Xu, Yan Zhang