Article
Neurosciences
Maria Venneri, Vanessa Vezzi, Annarita Di Mise, Marianna Ranieri, Mariangela Centrone, Grazia Tamma, Lene N. Nejsum, Giovanna Valenti
Summary: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked disease caused by gain-of-function mutations of arginine vasopressin receptor 2 (V2R). The constitutive AQP2 trafficking associated with the gain-of-function V2R-R137L/C mutants causing NSIAD is protein kinase A independent and requires an intact Ser269 in AQP2 under the control of ROCK phosphorylation.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Review
Medicine, General & Internal
Gheun-Ho Kim
Summary: Drug-induced hyponatremia caused by renal water retention is mainly classified into SIADH and NSIAD. Psychotropic agents, anticancer chemotherapeutic agents, and thiazide diuretics are the major causes. NSIAD, which involves the upregulation of AQP2, is the major mechanism for drug-induced hyponatremia.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jurgen Wess
Summary: Beta-arrestins play a dual role as inhibitors of signaling via G protein-coupled receptors and as signaling molecules themselves. Despite their structural and sequence homology, beta-arrestin-1 and -2 have distinct and non-redundant functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medical Laboratory Technology
Hok Fung Tong, Mei Tik Stella Leung, Chun Hei Toby Chan, Hoi Ning Cheung, Wing Lai Tony Mak, Pak Lam Sammy Chen
Summary: NSIAD is a rare inherited disorder characterized by hyponatremia, with diverse ethnic, genetic, and phenotypic presentations. Target analysis of R137C-V2R may aid in diagnosis in most cases, and genetic testing can confirm the diagnosis, motivate adherence to treatment, offer genotype-guided therapy, and allow cascade screening to prevent hyponatremia.
CLINICA CHIMICA ACTA
(2021)
Article
Physiology
Abigail Pearce, Theo Redfern-Nichols, Matthew Harris, David R. Poyner, Mark Wigglesworth, Graham Ladds
Summary: This study focused on the desensitisation of CLR-RAMP complexes in response to peptide agonists, finding different RAMP subunits have varying effects on beta-arrestin recruitment and internalisation, and that internalisation of CLR depends on beta-arrestin but is not required for full agonism. Overexpression of GRKs decreases receptor signalling by reducing surface expression of the CLR-RAMP complex. These findings provide a systematic analysis of the role of beta-arrestins and GRKs in CLR-RAMP signal transduction and open the door to further investigation into other Class B1 GPCRs.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Serena Milano, Fatima Maqoud, Monica Rutigliano, Ilenia Saponara, Monica Carmosino, Andrea Gerbino, Giuseppe Lucarelli, Michele Battaglia, Maria Svelto, Giuseppe Procino
Summary: This study discovered the functional expression of beta 3-AR in the renal tubule and its co-localization with the vasopressin receptor AVPR2. Activation of beta 3-AR triggers antidiuresis by increasing the expression of AQP2 and NKCC2 in renal cells. Treatment with the beta 3-AR agonist mirabegron increased the urinary excretion of AQP2 and NKCC2 in patients with overactive bladder syndrome. This suggests that mirabegron treatment may be able to bypass AVPR2 inactivation, induce antidiuresis, and correct polyuria in XNDI patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Physiology
Sua Kim, Chor Ho Jo, Gheun-Ho Kim
Summary: Hyponatremia is a common condition in clinical practice caused by renal water retention. Many medications can induce hyponatremia by affecting the release of arginine vasopressin or potentiating its action in the kidney. A major mechanism of drug-induced hyponatremia is the upregulation of AQP2 from V2R-cAMP-PKA signaling in the absence of AVP stimulation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Laura Szalai, Andras Sziraki, Laszlo Sandor Erdelyi, Kinga Bernadett Kovacs, Miklos Toth, Andras David Toth, Gabor Turu, Dominique Bonnet, Bernard Mouillac, Laszlo Hunyady, Andras Balla
Summary: In this study, a point mutation in the AVPR2 gene of a patient with nephrogenic diabetes insipidus (NDI) was identified, and the impaired function of the mutant receptor was characterized. The mutant receptor was primarily located in the endoplasmic reticulum (ER) and had reduced ability to generate cAMP in response to AVP stimulation. Pretreatment with pharmacochaperones partially restored the receptor's function. Both cell permeant agonists and antagonists can function as pharmacochaperones, providing a potential starting point for developing therapies for patients carrying this mutation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Verena Turco, Kira Pfleiderer, Jessica Hunger, Natalie K. Horvat, Kianush Karimian-Jazi, Katharina Schregel, Manuel Fischer, Gianluca Brugnara, Kristine Jaehne, Volker Sturm, Yannik Streibel, Duy Nguyen, Sandro Altamura, Dennis A. Agardy, Shreya S. Soni, Abdulrahman Alsasa, Theresa Bunse, Matthias Schlesner, Martina U. Muckenthaler, Ralph Weissleder, Wolfgang Wick, Sabine Heiland, Philipp Vollmuth, Martin Bendszus, Christopher B. Rodell, Michael O. Breckwoldt, Michael Platten
Summary: Glioblastoma, the most aggressive brain tumor type, can be treated by reprogramming myeloid cells using CDNP-R848 nanoparticles. CDNP-R848 induces tumor regression by targeting blood-borne macrophages independently of adaptive immunity.
NATURE COMMUNICATIONS
(2023)
Review
Medicine, General & Internal
Pajaree Krisanapan, Supawit Tangpanithandee, Charat Thongprayoon, Pattharawin Pattharanitima, Andrea Kleindienst, Jing Miao, Iasmina M. Craici, Michael A. Mao, Wisit Cheungpasitporn
Summary: This meta-analysis evaluates the safety and efficacy of vaptans in treating chronic hyponatremia in adult SIADH patients. The results indicate that vaptans effectively raise serum sodium concentration in the short-term, but caution is needed due to the risk of overcorrection.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Jean-Philippe Haymann
Summary: The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is characterized by impaired renal water dilution and impaired regulation of thirst center, after ruling out effective hypovolemia and corticotropin deficiency (Robertson, 2006).
ANNALES D ENDOCRINOLOGIE
(2023)
Article
Biochemistry & Molecular Biology
Claudia Sepulveda-Quinenao, Juan M. Rodriguez, Francisco Diaz-Castro, Andrea del Campo, Roberto Bravo-Sagua, Rodrigo Troncoso
Summary: The study investigates the impact of glucocorticoid receptor beta on glucose uptake and storage in hepatocytes, showing that GR beta overexpression inhibits the induction of gluconeogenic genes by dexamethasone and has insulin-like actions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Emily E. Blythe, Mark von Zastrow
Summary: A study found that the vasoactive intestinal peptide receptor 1 (VIPR1) does not require beta-arrestin for internalization or generation of endosomal signal. Instead, beta-arrestin desensitizes the plasma membrane phase without affecting the endosomal phase, resulting in sequential cAMP peaks. This finding challenges the current understanding that endosomal signaling is inherently beta-arrestin-dependent.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Medical Laboratory Technology
Amnon Schlegel
Summary: This report presents the first case of pathology-confirmed macroprolactinoma with syndrome of inappropriate antidiuresis (SIAD) that rapidly normalized water metabolism with dopamine agonist therapy. After 7 years, the patient still maintained normal sodium levels and prolactin levels.
LABORATORY MEDICINE
(2022)
Review
Physiology
Sai P. Pydi, Luiz E. Barella, Lu Zhu, Jaroslawna Meister, Mario Rossi, Jurgen Wess
Summary: Recent studies have identified the important roles of beta-Arrestin-1 and -2 in regulating glucose and energy homeostasis. Analysis of mutant mice revealed that these proteins play key roles in various cell types, resulting in significant changes in whole-body glucose and energy homeostasis. Furthermore, they exhibit distinct metabolic roles under physiological and patho-physiological conditions.
ANNUAL REVIEW OF PHYSIOLOGY
(2022)
Article
Cell Biology
Praveen Praveen, Martina Kocan, Adam Valkovic, Ross Bathgate, Mohammed Akhter Hossain
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2019)
Article
Genetics & Heredity
Isabel A. Hemming, Olivier Clement, Ivan E. Gladwyn-Ng, Hayley D. Cullen, Han Leng Ng, Heng B. See, Linh Ngo, Daniela Ulgiati, Kevin D. G. Pfleger, Mark Agostino, Julian I-T. Heng
Article
Biochemistry & Molecular Biology
Luning Yang, Alessandro D. Uboldi, Simona Seizova, Mary-Louise Wilde, Michael J. Coffey, Nicholas J. Katris, Yoshiki Yamaryo-Botte, Martina Kocan, Ross A. D. Bathgate, Rebecca J. Stewart, Malcolm J. McConville, Philip E. Thompson, Cyrille Y. Botte, Christopher J. Tonkin
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Urology & Nephrology
Bryna S. M. Chow, Martina Kocan, Matthew Shen, Yan Wang, Lei Han, Jacqueline Y. Chew, Chao Wang, Sanja Bosnyak, Katrina M. Mirabito-Colafella, Giannie Barsha, Belinda Wigg, Elizabeth K. M. Johnstone, Mohammed A. Hossain, Kevin D. G. Pfleger, Kate M. Denton, Robert E. Widdop, Roger J. Summers, Ross A. D. Bathgate, Tim D. Hewitson, Chrishan S. Samuel
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2019)
Article
Multidisciplinary Sciences
Leopold Duerrauer, Edin Muratspahic, Jasmin Gattringer, Peter Keov, Helen C. Mendel, Kevin D. G. Pfleger, Markus Muttenthaler, Christian W. Gruber
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Amanat Ali, Elizabeth K. M. Johnstone, Bincy Baby, Heng B. See, Angela Song, K. Johan Rosengren, Kevin D. G. Pfleger, Mohammed Akli Ayoub, Ranjit Vijayan
Summary: The study demonstrated the allosteric effect of LVV-H7 on AngII binding, showing that LVV-H7 can enhance the binding of AngII to AT1R through an allosteric mechanism, supporting the pharmacological targeting of AT1R by hemorphins for potential implications in vascular and renal physiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Elizabeth K. M. Johnstone, Heng B. See, Rekhati S. Abhayawardana, Angela Song, K. Johan Rosengren, Stephen J. Hill, Kevin D. G. Pfleger
Summary: Receptor heteromerization involves complex formation between at least two different receptors with distinct pharmacology, necessitating the use of Receptor-HIT technology for detection and analysis of pharmacological functions. This study for the first time utilized BRET and fluorescently-labeled ligands to investigate receptor heteromerization on the cell surface effectively.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Carl W. White, Laura E. Kilpatrick, Kevin D. G. Pfleger, Stephen J. Hill
Summary: The study demonstrates a sensitive real-time approach to quantify secretion and receptor binding of native chemokines in live cells for better understanding of their molecular interactions and function. By using CRISPR/Cas9 genome editing to tag chemokine CXCL12 with nanoluciferase fragment HiBiT, the secretion and binding of chemokines can be monitored and quantified. These live cell approaches combine the sensitivity of nanoluciferase with CRISPR/Cas9 genome editing to detect, quantify, and monitor binding of low levels of native secreted proteins in real time.
Review
Cell Biology
Sipin Zhu, Mei Liu, Samuel Bennett, Ziyi Wang, Kevin D. G. Pfleger, Jiake Xu
Summary: CCL2 is an inflammatory mediator that recruits immune cells and plays a crucial role in skeletal biology and diseases. Its interaction with CCR2 activates multiple signaling cascades affecting the skeletal system.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Emily Golden, Rabab Rashwan, Eleanor A. Woodward, Agustin Sgro, Edina Wang, Anabel Sorolla, Charlene Waryah, Wan Jun Tie, Elisabet Cuyas, Magdalena Ratajska, Iwona Kardas, Piotr Kozlowski, Elizabeth K. M. Johnstone, Heng B. See, Ciara Duffy, Jeremy Parry, Kim A. Lagerborg, Piotr Czapiewski, Javier A. Menendez, Adam Gorczynski, Bartosz Wasag, Kevin D. G. Pfleger, Christina Curtis, Bum-Kyu Lee, Jonghwan Kim, Joseph Cursons, Nathan J. Pavlos, Wojciech Biernat, Mohit Jain, Andrew J. Woo, Andrew Redfern, Pilar Blancafort
Summary: AAMDC, a frequently amplified gene in ER+ breast cancer, regulates metabolic enzymes, controls PI3K-AKT-mTOR signaling, and shows sensitivity to combination therapy with anti-estrogens, potentially serving as a target for selective blockers in malignancies.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Elizabeth K. M. Johnstone, Rekhati S. Abhayawardana, Heng B. See, Ruth M. Seeber, Shannon L. O'Brien, Walter G. Thomas, Kevin D. G. Pfleger
Summary: TRIO acts as an intermediate in the transactivation process of EGFR mediated by AngII/AT(1) receptor, with its proximity to other proteins confirmed through BRET assays. The existence of the AT(1)-EGFR heteromer was further supported by Receptor-Heteromer Investigation Technology, revealing potential mechanisms of TRIO contribution to this process.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Elizabeth K. M. Johnstone, Kevin D. G. Pfleger
Summary: Receptor heteromers, formed through heteromerisation of receptors, present new drug targets with potential for increased specificity. The Receptor-HIT technology enables real-time detection of heteromers and provides functional information for pharmacological quantification, supporting drug development efforts.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Multidisciplinary Sciences
Natalia G. Sampaio, Lise Chauveau, Jonny Hertzog, Anne Bridgeman, Gerissa Fowler, Jurgen P. Moonen, Maeva Dupont, Rebecca A. Russell, Marko Noerenberg, Jan Rehwinkel
Summary: Research has identified MDA5 as a cellular sensor for SARS-CoV-2 infection that induces type I and III IFNs, which can inhibit viral replication, but does not affect the induction of IL6 and TNF.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Carl W. White, Birgit Caspar, Hannah K. Vanyai, Kevin D. G. Pfleger, Stephen J. Hill
CELL CHEMICAL BIOLOGY
(2020)
Article
Pharmacology & Pharmacy
Bradley L. Hoare, Martina Kocan, Shoni Bruell, Daniel J. Scott, Ross A. D. Bathgate
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2019)