Article
Biochemistry & Molecular Biology
Muhammad Yasir Asghar, Taru Lassila, Ilkka Paatero, Van Dien Nguyen, Pauliina Kronqvist, Jixi Zhang, Anna Slita, Christoffer Lof, You Zhou, Jessica Rosenholm, Kid Tornquist
Summary: Research shows that STIM1 and ORAI1 are upregulated in thyroid cancer, and their knockdown can attenuate SOCE, reduce invasion and expression of promigratory factors, inhibit cell proliferation, and increase sensitivity to chemotherapeutic drugs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Christian Sirko, Matthew J. Novello, Peter B. Stathopulos
Summary: Stromal interaction molecule 1 (STIM1) is a calcium sensing protein that regulates store-operated calcium entry. S-Glutathionylation of STIM1 at Cys49 or Cys56 induces conformational changes and thermodynamic destabilization. This modification or mutation of Cys56 reduces the binding affinity to calcium ions.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Goutham Kodakandla, Savannah J. West, Qiaochu Wang, Ritika Tewari, Michael X. Zhu, Askar M. Akimzhanov, Darren Boehning
Summary: Cell surface stimuli can induce the release of calcium from the endoplasmic reticulum to regulate cellular physiology. The S-acylation of Orai1 and STIM1 proteins plays a critical role in the assembly and function of CRAC channels.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ferdinand Horvath, Sascha Berlansky, Lena Maltan, Herwig Grabmayr, Marc Fahrner, Isabella Derler, Christoph Romanin, Thomas Renger, Heinrich Krobath
Summary: STIM1 is a protein located in the endoplasmic reticulum (ER) membrane that senses the concentration of calcium ions and plays a role in the activation of calcium channels. Through molecular docking simulations, a structural model of the resting state of STIM1 was established, and the binding interface was analyzed using molecular dynamics simulations. Experimental results confirmed the validity of the model and provided insights into the conformational dynamics of the resting state of STIM1.
Article
Pharmacology & Pharmacy
Xiaoman Yuan, Bin Tang, Yilan Chen, Lijuan Zhou, Jingwen Deng, Lin Han, Yonggong Zhai, Yandong Zhou, Donald L. Gill, Chuanjian Lu, Youjun Wang
Summary: Celastrol, a natural compound, is identified as a novel SOCE inhibitor. It ameliorates skin lesions and reduces PASI scores in psoriasis-like mice by inhibiting Ca2+ entry through its actions on STIM1 and Orai1. These findings suggest that the SOCE pathway may serve as a new druggable target for treating psoriasis.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Christina Humer, Christoph Romanin, Carmen Hoeglinger
Summary: Orai1, a Ca2+-selective pore in the plasma membrane, is crucial for maintaining Ca2+ homeostasis within a cell. In addition to its C-terminus, the second loop and N-terminus of Orai1 play a multifaceted role in the functioning of CRAC channels.
Review
Biochemistry & Molecular Biology
Ningxia Zhang, Hongming Pan, Xiaojing Liang, Jiansheng Xie, Weidong Han
Summary: Store-operated Ca2+ entry (SOCE) is a major calcium signaling pathway that regulates various biological processes. TMEM family proteins, including STIM and ORAI, play essential roles in SOCE. TMEM proteins are a large family of transmembrane proteins that span biological membranes. However, the functional knowledge about TMEM proteins is still limited.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Hadas Achildiev Cohen, Elia Zomot, Tomer Nataniel, Ruslana Militsin, Raz Palty
Summary: Depletion of Ca2+ from the endoplasmic reticulum (ER) leads to the formation of ER-PM membrane contact sites (MCSs) by the ER Ca2+ sensor STIM1. STIM1 binds to Orai channels at the ER-PM MCS, resulting in cellular Ca2+ entry. Previous studies suggested that STIM1 interacts with the plasma membrane (PM) and Orai1 using separate modules, but this study reveals that the oligomerization of the STIM-Orai activation region (SOAR) promotes direct interaction with PM phosphoinositides to trap STIM1 at ER-PM MCSs. This molecular mechanism is co-regulated by the STIM1 coil-coiled 1 and inactivation domains.
Article
Physiology
Yi-Ting Huang, Ya-Ting Hsu, Yih-Fung Chen, Meng-Ru Shen
Summary: Store-operated Ca2+ entry (SOCE) is essential for cellular functions, with STIM1 playing a crucial role in this process. STIM1 mutations have been shown to impact cancer cell behavior, with specific variants affecting focal adhesion turnover, Ca2+ influx during SOCE, and cell migration, suggesting potential therapeutic implications.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Immunology
Lifei Hou, Koichi Yuki
Summary: This study found that CD4 T cells with cytotoxic properties in experimental autoimmune encephalomyelitis (EAE) were positive for both CXCR6 and CCR6 markers. The CD4 T cells infiltrating the spinal cord showed high cytotoxicity, expressing Granzyme(s), IFN gamma, and GM-CSF. These findings highlight the importance of cytotoxicity in EAE pathology.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Chinmayee Das, Mathilakath M. Vijayan
Summary: Glucocorticoids can rapidly elicit cell signaling independent of the activation of glucocorticoid receptor (GR) as a transcription factor. The mechanism for this rapid nongenomic signaling involves the translocation of intracellular GR to the plasma membrane, which is mediated by the entry of extracellular calcium. This rapid action of cortisol may enhance cellular sensitivity to nongenomic signaling through membrane-anchored GR.
Article
Multidisciplinary Sciences
Ronald Udasin, Anwesha Sil, Elia Zomot, Hadas Achildiev Cohen, Jozafina Haj, Nurit Engelmayer, Shaya Lev, Alexander M. Binshtok, Yuval Shaked, Michael A. Kienzler, Raz Palty
Summary: This study reports the synthesis and characterization of azoboronate light-operated CRAG channel inhibitors (LOCIs), which enable dynamic and reversible remote modulation of native CRAG channels using light. The application of LOCI-1 was demonstrated in gene expression regulation in T lymphocytes, cancer cell seeding at metastatic sites, and pain-related behavior.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Adriana M. Fresquez, Carl White
Summary: The gaseous signaling molecule hydrogen sulfide (H2S) selectively modifies Orai3 by regulating the cysteines 226 and 232 residues, which limits the occurrence of store-operated calcium entry (SOCE).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Immunology
Junjie Zhao, Yun Liao, William Miller-Little, Jianxing Xiao, Caini Liu, Xiaoxia Li, Xiao Li, Zizhen Kang
Summary: This study identified STEAP4 as a Th17-specific effector molecule that plays a key role in the pathogenesis of neuroinflammation. STEAP4 knockout mice showed delayed onset and reduced severity of EAE induced by active immunization. Notably, STEAP4 was only induced in the spinal cord of EAE mice that received Th17 cells, indicating its specific role in Th17-mediated neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Endocrinology & Metabolism
Jian Qiu, Martha A. Bosch, Todd L. Stincic, Avery C. Hunker, Larry S. Zweifel, Oline K. Ronnekleiv, Martin J. Kelly
Summary: This study reveals the critical role of STIM1 in modulating glutamatergic activation of TRPC 5 channels in POMC neurons, which is essential for maintaining energy balance.
MOLECULAR METABOLISM
(2022)
Article
Multidisciplinary Sciences
Larissa Bendiks, Fabienne Geiger, Thomas Gudermann, Stefan Feske, Alexander Dietrich
SCIENTIFIC REPORTS
(2020)
Article
Medicine, Research & Experimental
Sascha Kahlfuss, Ulrike Kaufmann, Axel R. Concepcion, Lucile Noyer, Dimitrius Raphael, Martin Vaeth, Jun Yang, Priya Pancholi, Mate Maus, James Muller, Lina Kozhaya, Alireza Khodadadi-Jamayran, Zhengxi Sun, Patrick Shaw, Derya Unutmaz, Peter B. Stathopulos, Cori Feist, Scott B. Cameron, Stuart E. Turvey, Stefan Feske
EMBO MOLECULAR MEDICINE
(2020)
Article
Multidisciplinary Sciences
Ga-Yeon Son, Krishna Prasad Subedi, Hwei Ling Ong, Lucile Noyer, Hassan Saadi, Changyu Zheng, Rajesh Bhardwaj, Stefan Feske, Indu Suresh Ambudkar
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Editorial Material
Multidisciplinary Sciences
Liwei Wang, Stefan Feske
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Physics, Condensed Matter
Wilken Seemann, Alexander Kothe, Christian Tessarek, Gesa Schmidt, Siqi Qiao, Nils von den Driesch, Jan Wiersig, Alexander Pawlis, Gordon Callsen, Jurgen Gutowski
Summary: Microdisk resonators, with their small mode volume, are investigated for low-threshold lasing and efficient single-photon sources. Analysis of ZnSe-based microdisks with ZnCdSe quantum well structures demonstrates stimulated emission into whispering gallery modes. Scanning electron microscopy reveals a correlation between edge roughness and optical quality, confirmed by calculations based on measured roughness.
PHYSICA STATUS SOLIDI B-BASIC SOLID STATE PHYSICS
(2021)
Editorial Material
Cell Biology
Lucile Noyer, Stefan Feske
Article
Immunology
Axel R. Concepcion, Larry E. Wagner, Jingjie Zhu, Anthony Y. Tao, Jun Yang, Alireza Khodadadi-Jamayran, Yin-Hu Wang, Menghan Liu, Rebecca E. Rose, Drew R. Jones, William A. Coetzee, David Yule, Stefan Feske
Summary: LRRC8C is a critical component of VRAC in T cells, mediating the transport of 2'3' cGAMP and activating the STING-p53 signaling pathway. Its deletion enhances T cell function and increases T cell-dependent immune responses.
Article
Immunology
Gesine Behrens, Stephanie L. Edelmann, Timsse Raj, Nina Kronbeck, Thomas Monecke, Elena Davydova, Elaine H. Wong, Lisa Kifinger, Florian Giesert, Martin E. Kirmaier, Christine Hohn, Laura S. de Jonge, Mariano Gonzalez Pisfil, Mingui Fu, Sebastian Theurich, Stefan Feske, Naoto Kawakami, Wolfgang Wurst, Dierk Niessing, Vigo Heissmeyer
Summary: The proteins Roquin-1 and Regnase-1 play crucial roles in maintaining immune homeostasis, with mutations leading to systemic lupus erythematosus-like phenotypes and autoimmunity. Additionally, these mutations affect T cell activation, metabolic reprogramming, and autoimmunity processes.
Article
Multidisciplinary Sciences
Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Y. Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Boram Lee, Amy Lee, Johannes W. Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske
Summary: The regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Marilena Letizia, Yin-Hu Wang, Ulrike Kaufmann, Lorenz Gerbeth, Annegret Sand, Max Brunkhorst, Patrick Weidner, Joern Felix Ziegler, Chotima Boettcher, Stephan Schlickeiser, Camila Fernandez, Megumi Yamashita, Kenneth Stauderman, Katherine Sun, Desiree Kunkel, Murali Prakriya, Ashley D. Sanders, Britta Siegmund, Stefan Feske, Carl Weidinger
Summary: Inflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune responses. This study found that store-operated Ca2+ entry (SOCE) regulates the function of immune cells in the lamina propria of IBD patients. Inhibiting SOCE reduced the production of proinflammatory cytokines, suggesting that targeting SOCE may be a potential treatment for IBD.
EMBO MOLECULAR MEDICINE
(2022)
Article
Physiology
Liwei Wang, Lucile Noyer, Yin-Hu Wang, Anthony Y. Tao, Wenyi Li, Jingjie Zhu, Pedro Saavedra, Syed T. Hoda, Jun Yang, Stefan Feske
Summary: Despite its expression in immune cells, ORAI3 appears to be dispensable or redundant for physiological and pathological immune responses mediated by these cells.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Immunology
Taku Ito-Kureha, Cristina Leoni, Kayla Borland, Giulia Cantini, Marian Bataclan, Rebecca N. Metzger, Gregor Ammann, Anne B. Krug, Annalisa Marsico, Stefanie Kaiser, Stefan Canzar, Stefan Feske, Silvia Monticelli, Julian Koenig, Vigo Heissmeyer
Summary: The m(6)A modification plays a crucial role in the development, activation and survival of T cells. The Wtap protein is essential for m(6)A methyltransferase complex function and is crucial in TCR signaling. m(6)A modification destabilizes Orai1 and Ripk1 mRNAs, impacting the survival of T cells.
Article
Multidisciplinary Sciences
Yin -Hu Wang, Lucile Noyer, Sascha Kahlfuss, Dimitrius Raphael, Anthony Y. Tao, Ulrike Kaufmann, Jingjie Zhu, Marisa Mitchell-Flack, Ikjot Sidhu, Fang Zhou, Martin Vaeth, Paul G. Thomas, Sean P. Saunders, Kenneth Stauderman, Maria A. Curotto de Lafaille, Stefan Feske
Summary: The study reveals that SOCE through CRAC channels plays a crucial role in regulating T cell function, particularly in TH2 cells, by controlling the expression of transcription factors and cytokines. Inhibition of SOCE shows potential as a treatment for allergic airway disease.
Article
Biology
Scott M. Emrich, Ryan E. Yoast, Xuexin Zhang, Adam J. Fike, Yin-Hu Wang, Kristen N. Bricker, Anthony Y. Tao, Ping Xin, Vonn Walter, Martin T. Johnson, Trayambak Pathak, Adam C. Straub, Stefan Feske, Ziaur S. M. Rahman, Mohamed Trebak
Summary: This study reveals that Orai3 and Orai1 mediate native CRAC channels in B cells during activation, and the combined loss of both isoforms impairs various functions in B cells, including SOCE, proliferation, survival, NFAT activation, mitochondrial respiration, glycolysis, and metabolic reprogramming. However, the deletion of Orai1 and Orai3 does not affect humoral immunity to influenza A virus infection in mice, suggesting the presence of other co-stimulatory signals that compensate for the requirement of BCR-mediated CRAC channel function in B cells. These findings provide important insights into the physiological roles of Orai1 and Orai3 proteins in SOCE and effector functions of B lymphocytes.
Meeting Abstract
Immunology
Marilena Letizia, Ulirike Kaufmann, Lorenz Gerbeth, Annegret Sand, Max Brunkhorst, Yinhu Wang, Chotima Boettcher, Stephan Schlickeiser, Camila Fernandez Zapata, Desiree Kunkel, Britta Siegmund, Stefan Feske, Carl Weidinger
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)