Article
Cell Biology
Takuto Fujii, Mizuki Katoh, Manami Ootsubo, Oanh T. T. Nguyen, Mayumi Iguchi, Takahiro Shimizu, Yoshiaki Tabuchi, Yasuharu Shimizu, Hiroshi Takeshima, Hideki Sakai
Summary: CGs can inhibit glucose metabolism of cancer cells by inhibiting Na+,K+-ATPase and decreasing the expression of GLUT1. The binding of CGs with intracellular alpha 3NaK elicits NAADP-mediated calcium mobilization.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Julia Weikum, Jeroen F. van Dyck, Saranya Subramani, David P. Klebl, Merete Storflor, Stephen P. Muench, Soren Abel, Frank Sobott, J. Preben Morth
Summary: The study reveals the complex interaction between bacterial magnesium transporter A (MgtA) and cardiolipin 18:1 and cardiolipin 16:0, highlighting the importance of lipid environment in protein activity and stability. Further understanding of Mg2+ homeostasis in bacteria will provide insights into bacterial infections.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Plant Sciences
Magda F. El-Adl, Taha M. El-Katony, Reham M. Nada
Summary: The study found that the specific ion effects of Na+ and K+ were different on the growth of Ulva lactuca. Ulva lactuca showed better growth with high concentrations of NaCl, while KCl might have adverse effects on photosynthesis and cell wall. Transcription of PM H+-ATPase was induced specifically by high concentrations of Na+, while the induction of PM-Na+/K+-ATPase-like alone could not improve the growth of KCl-treated Ulva lactuca.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Declan Williams, Mohadeseh Mehrabian, Hamza Arshad, Shehab Eid, Christopher Sackmann, Wenda Zhao, Xinzhu Wang, Farinaz Ghodrati, Claire E. Verkuyl, Joel C. Watts, Gerold Schmitt-Ulms
Summary: This study investigated the molecular environment of prion protein in the brain, revealing significant interactions between cellular Na,K-ATPases (NKAs) and cellular PrP (PrPC), suggesting that the activity of NKAs may impact the pathobiology of prion diseases.
Article
Biochemistry & Molecular Biology
Alexei A. Adzhubei, Anna P. Tolstova, Maria A. Strelkova, Vladimir A. Mitkevich, Irina Yu Petrushanko, Alexander A. Makarov
Summary: Alzheimer's disease (AD) is a neurodegenerative disease characterized by disrupted neuronal properties and loss, affecting cognitive and memory functions. The interaction between Na,K-ATPase and beta amyloid (A beta) is important in AD pathogenesis. This study used molecular modeling to identify interaction sites between A beta(42) isoforms and Na,K-ATPase, providing insights for potential inhibitors. The findings contribute to understanding the underlying mechanisms and developing targeted interventions for AD.
Article
Plant Sciences
Qi Chen, Kai Xu, Yan Xu, Dehua Ji, Changsheng Chen, Chaotian Xie, Wenlei Wang
Summary: This study analyzed the function of Na+/K+-ATPase in the response of Neoporphyra haitanensis to salt stress and found that it played a crucial role in maintaining the K+/Na+ homeostasis in the algae. The inhibitor ouabain caused Na+ accumulation and K+ leakage in the cells, disrupting the K+/Na+ balance and leading to decreased photosynthesis and oxidative damage in the algae.
FRONTIERS IN PLANT SCIENCE
(2023)
Review
Cell Biology
Xiaoyan Zhang, Weithye Lee, Jin-Song Bian
Summary: Na+/K+-ATPase is a large transmembrane protein expressed in most eukaryotic cell plasma membranes, maintaining various cellular functions. The protective effect of NKA against neurodegenerative diseases has gradually emerged in recent decades, which is crucial for understanding the pathophysiology of these diseases and identifying new therapeutic targets.
Article
Biochemistry & Molecular Biology
Marlene U. Fruergaard, Ingrid Dach, Jacob L. Andersen, Mette Ozol, Azadeh Shahsavar, Esben M. Quistgaard, Hanne Poulsen, Natalya U. Fedosova, Poul Nissen
Summary: In this study, the crystal structure and functional properties of the E2-BeFx complex of pig kidney Na+,K+-ATPase are investigated. The complex resembles the E2P intermediate and is able to bind ADP/ATP and Na+. The results suggest a relation between E2-BeFx and the E*P intermediate in the functional cycle of Na+, K+-ATPase.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Santiago E. Faraj, Wanda M. Valsecchi, Mariela Ferreira-Gomes, Mercedes Centeno, Elina Malen Saint Martin, Natalya U. Fedosova, Juan Pablo FC. Rossi, Monica R. Montes, Rolando C. Rossi
Summary: The Na+/K+-ATPase is a plasma membrane glycoprotein that exchanges intracellular Na+ for extracellular K+ by hydrolyzing ATP. The asymmetric distribution of Na+ and K+ is essential for cellular life. Current research indicates that Na+ becomes spontaneously occluded in the E1 dephosphorylated form of the Na+/K+-ATPase, showing positive interactions between binding sites. Adding ATP does not increase Na+ occlusion.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Review
Microbiology
Cassiano Felippe Goncalves-de-Albuquerque, Carolina Medina Coeli da Cunha, Leo Victor Grimaldi de Castro, Caroline de Azevedo Martins, Marcos Roberto Colombo Barnese, Patricia Burth, Mauricio Younes-Ibrahim
Summary: In 1915, Inada and Ido identified Leptospira sp. as the pathogen responsible for Weil's Disease, which was later confirmed to cause leptospirosis. The molecular mechanisms and interactions between bacterial components and the host, as well as the systemic dysfunctions, still need to be fully understood. Leptospirosis affects all animal species and involves a cellular mechanism common to all eukaryotes. Na/K-ATPase is targeted by the leptospiral endotoxin, leading to dysfunctions and organ disorders. Additionally, metabolic disorders and inflammatory responses are triggered during leptospirosis, involving various molecular mechanisms. Na/K-ATPase plays a critical role in the disease and can be a potential therapeutic target or an indicator of disease severity.
Article
Cell Biology
Bruno Sterlini, Alessandra Romei, Chiara Parodi, Davide Aprile, Michele Oneto, Anita Aperia, Pierluigi Valente, Flavia Valtorta, Anna Fassio, Pietro Baldelli, Fabio Benfenati, Anna Corradi
Summary: This study reveals that PRRT2 deficiency affects the function of Na+/K+ ATPase (NKA) in neurons, leading to increased clustering of NKA on the plasma membrane, which can be reversed by re-expression of PRRT2. Additionally, PRRT2 deficiency also reduces the NKA-dependent afterhyperpolarization in neurons following high-frequency firing.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Rawad Hodeify, Sawsan Kreydiyyeh, Leen Mohammad Jamal Zaid
Summary: The sodium-potassium pump (NKA) consumes a significant amount of energy in animal cells for creating electrochemical gradients of sodium and potassium ions. The regulation of its activity, including its expression, localization, enzymatic activity, and interactions with other proteins, is crucial. However, the mechanisms controlling the trafficking of NKA between the cell membrane and intracellular compartments are poorly understood. This review summarizes previous studies on the regulation of NKA trafficking and its potential endocytic signals, as well as highlights recent research on NKA trafficking and modulation in various cells.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Parasitology
Xiao-Fei Shang, Xiao-Lou Miao, Li-Xia Dai, Yu Wang, Bing Li, Hu Pan, Ji-Yu Zhang
Summary: This study confirmed the strong acaricidal activity and inhibitory effect on Na+-K+-ATPase of the novel strophanthidin derivative QXG-1. By chemically modifying specific positions of the strophanthidin molecule, its toxicity against mites can be controlled. The safety of QXG-1 in vitro and in vivo also suggests its potential as a promising acaricidal agent.
VETERINARY PARASITOLOGY
(2021)
Article
Immunology
Jin Zheng, Ping Lan, Meihe Li, Min-chao Kang, Meng Xun, Xiangyun Ma, Mengyao Yan, Dan Sun, Yu Shen, Xinyi Fu, Xiaoming Ding, Xiaofei Yan, Wu-jun Xue
Summary: Reduced Na+/K+-ATPase (NKA) activity and NKA alpha 1 expression are implicated in the pathogenesis of renal diseases. NKA alpha 1 deficiency exacerbates tubulointerstitial lesions and fibrosis in a mouse model of UUO. Activation of NKA alpha 1 by an antibody against its extracellular DR region (DRm217) prevents UUO-induced tubulointerstitial lesions, preserves kidney function, and reduces renal fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Lucy Kate Ladefoged, Birgit Schiott, Natalya U. Fedosova
Summary: The study reveals significant differences in the binding properties of different subfamilies of cardiotonic steroids with the Na+,K+-ATPase. While bufadienolides show beneficial effects with K+, they differ from cardenolides which have an antagonistic relationship with K+. Through simulations, it was found that the binding of bufadienolides is influenced by amino acid coordination patterns and the presence of cations, illustrating the complex interplay of factors in these interactions.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Michael Habeck, Elmira Tokhtaeva, Yotam Nadav, Efrat Ben Zeev, Sean P. Ferris, Randal J. Kaufman, Elizabeta Bab-Dinitz, Jack H. Kaplan, Laura A. Dada, Zvi Farfel, Daniel M. Tal, Adriana Katz, George Sachs, Olga Vagin, Steven J. D. Karlish
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Flemming Cornelius, Naoki Tsunekawa, Chikashi Toyoshima
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Multidisciplinary Sciences
Yoshiyuki Norimatsu, Kazuya Hasegawa, Nobutaka Shimizu, Chikashi Toyoshima
Article
Multidisciplinary Sciences
Michael Habeck, Einat Kapri-Pardes, Michal Sharon, Steven J. D. Karlish
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Multidisciplinary Sciences
Xingya Xu, Ryuta Kanai, Norihiko Nakazawa, Li Wang, Chikashi Toyoshima, Mitsuhiro Yanagida
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Multidisciplinary Sciences
Naoki Tsunekawa, Haruo Ogawa, Junko Tsueda, Toshihiko Akiba, Chikashi Toyoshima
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Multidisciplinary Sciences
Yoshiki Kabashima, Haruo Ogawa, Rie Nakajima, Chikashi Toyoshima
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Ryuta Kanai, Flemming Cornelius, Haruo Ogawa, Kanna Motoyama, Bente Vilsen, Chikashi Toyoshima
Summary: The sodium pump (Na+, K+-ATPase, NKA) is crucial for maintaining ion gradients across cell membranes, with cardiotonic steroids (CTSs) acting as specific inhibitors. Different structural features of CTSs result in diverse inhibitory properties, with crystal structures providing insights into their mechanism of action and potential for isoform specific targeting.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Editorial Material
Physiology
Michael Habeck, Hanne Poulsen
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Takaharu Sakuragi, Ryuta Kanai, Akihisa Tsutsumi, Hirotaka Narita, Eriko Onishi, Kohei Nishino, Takuya Miyazaki, Takeshi Baba, Hidetaka Kosako, Atsushi Nakagawa, Masahide Kikkawa, Chikashi Toyoshima, Shigekazu Nagata
Summary: Xkr8-Basigin is a plasma membrane phospholipid scramblase activated by kinases or caspases. The structure revealed key charged residues essential for its scrambling activity, with phosphatidylcholine binding in a hydrophobic cleft on the surface. The tryptophan residue between the head group of phosphatidylcholine and the extracellular end plays a crucial role in regulating the scramblase activity.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Ryuta Kanai, Flemming Cornelius, Bente Vilsen, Chikashi Toyoshima
Summary: Cryo-electron microscopy was used to study the structure of Na+, K+-ATPase and its variations. The results showed that different reaction states exhibited different biochemical characteristics, and the presence of Mg2+ ions in the transmembrane cation binding sites played a crucial role in the reactions. The binding mechanism of the new-generation cardiotonic steroids (CTSs) did not significantly affect the structure of NKA, and the phospholipid molecules were better resolved in the electron microscopy maps compared to X-ray structures.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Caroline Neumann, Lena Lindtoft Rosenbaek, Rasmus Kock Flygaard, Michael Habeck, Jesper Lykkegaard Karlsen, Yong Wang, Kresten Lindorff-Larsen, Hans Henrik Gad, Rune Hartmann, Joseph Anthony Lyons, Robert A. Fenton, Poul Nissen
Summary: The sodium-potassium-chloride transporter NKCC1 is a crucial protein involved in ion uptake across plasma membranes. This study presents the cryo-electron microscopy structure of human NKCC1 and provides insights into its functional mechanism. The findings have implications for understanding the structure-function relationship of NKCC1 and other related proteins.
Review
Biochemistry & Molecular Biology
Charlott Stock, Tomas Heger, Sara Basse Hansen, Sigrid Thirup Larsen, Michael Habeck, Thibaud Dieudonne, Ronja Driller, Poul Nissen
Summary: P-type ATPases are essential for maintaining electrochemical gradients, controlling membrane lipid asymmetry, and mediating intricate signaling networks. Cryo-EM analysis has significantly advanced our understanding of P-type ATPases, revealing new structures, mechanisms, and modes of regulation. This review highlights the progress in the field, focusing on unique features found in the five subfamilies.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Biochemistry & Molecular Biology
Ryuta Kanai, Bente Vilsen, Flemming Cornelius, Chikashi Toyoshima
Summary: Na+,K+-ATPase (NKA) plays a crucial role in establishing electrochemical gradients for Na+ and K+ across the cell membrane. This study presents two crystal structures of NKA in different states, providing insight into its reaction cycle and functional roles. The findings demonstrate how NKA converts between different forms and utilizes the lipid bilayer for gating the ion pathway.
Article
Physiology
Natalya U. Fedosova, Michael Habeck, Poul Nissen
Summary: This article provides an overview of the well-established biochemical properties of Na,K-ATPase, focusing on its isoforms, transport mechanism and principle conformations, inhibitors, and insights gained from crystal structures.
COMPREHENSIVE PHYSIOLOGY
(2022)