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.
Article
Multidisciplinary Sciences
Dorian Ziegler, David Vindrieux, Delphine Goehrig, Sara Jaber, Guillaume Collin, Audrey Griveau, Clotilde Wiel, Nadia Bendridi, Sophia Djebali, Valerio Farfariello, Natacha Prevarskaya, Lea Payen, Jacqueline Marvel, Sebastien Aubert, Jean-Michel Flaman, Jennifer Rieusset, Nadine Martin, David Bernard
Summary: The lack of ITPR2 in mice leads to improved aging, which is associated with a decreased number of contacts between mitochondria and endoplasmatic reticulum.
NATURE COMMUNICATIONS
(2021)
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
Biochemical Research Methods
S. Wenceslao Evans, Dong-Qing Shi, Mariya Chavarha, Mark H. Plitt, Jiannis Taxidis, Blake Madruga, Jiang Lan Fan, Fuu-Jiun Hwang, Siri C. van Keulen, Carl-Mikael Suomivuori, Michelle M. Pang, Sharon Su, Sungmoo Lee, Yukun A. Hao, Guofeng Zhang, Dongyun Jiang, Lagnajeet Pradhan, Richard H. Roth, Yu Liu, Conor C. Dorian, Austin L. Reese, Adrian Negrean, Attila Losonczy, Christopher D. Makinson, Sui Wang, Thomas R. Clandinin, Ron O. Dror, Jun B. Ding, Na Ji, Peyman Golshani, Lisa M. Giocomo, Guo-Qiang Bi, Michael Z. Lin
Summary: By inverting the fluorescence-voltage relationship, the photostability of ASAP family genetically encoded voltage indicators (GEVIs) has been enhanced. Two improved GEVIs, ASAP4b and ASAP4e, enable single-trial detection and recording in standard one- and two-photon microscopes with better temporal resolution. They can simultaneously detect voltage and calcium signals and extend the duration of voltage recordings.
Review
Cell Biology
Inbal Dagan, Raz Palty
Summary: Calcium signaling in cells plays a crucial role in regulating cell survival, proliferation, and death. Store-operated Ca2+ entry through CRAC channels is a major pathway for Ca2+ influx in non-excitable cells, regulated by a negative feedback mechanism called slow Ca2+ dependent inactivation (SCDI).
Article
Multidisciplinary Sciences
Donghoon Han, Si-Hyuck Kang, Chang-Hwan Yoon, Tae-Jin Youn, In-Ho Chae
Summary: This study investigated the efficacy of intracoronary administration of EDTA as an adjunctive treatment to reduce ischemia-reperfusion (IR) injury in a swine model. The results showed that EDTA significantly reduced infarct size, mitochondrial damage, and post-infarct remodeling. Further clinical studies are warranted to evaluate the efficacy of EDTA in patients with ST-segment elevation myocardial infarction.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Ghassan Bkaily, Danielle Jacques
Summary: Calcium is a positively charged ionic species that regulates various cell functions and acts as a second messenger. Abnormal calcium homeostasis can lead to diseases such as cardiovascular disorders, skeletal disorders, immune disorders, secretion disorders, and cancer. Therefore, pharmacological control of calcium transport is important in treating these conditions, particularly in the cardiovascular system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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
Multidisciplinary Sciences
Lei Yang, Rong-Chang Li, Bin Xiang, Yi-Chen Li, Li-Peng Wang, Yun-Bo Guo, Jing-Hui Liang, Xiao-Ting Wang, Tingting Hou, Xin Xing, Zeng-Quan Zhou, Haihong Ye, Ren-Qing Feng, Edward G. Lakatta, Zhen Chai, Shi-Qiang Wang
Summary: The contraction of heart cells is regulated by the signaling interaction between LCCs and RyRs, which is influenced by the nanodistance between JPH2 in the SR and CAV3 in the TT. Our study revealed that SRF and myocardin concurrently regulate the expression of JPH2 and CAV3, leading to enhanced efficiency of LCC-RyR signaling and compensation for LCC down-regulation during hibernation, maintaining heart power and avoiding calcium overload.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Cell Biology
Lena Maltan, Hadil Najjar, Adela Tiffner, Isabella Derler
Summary: Calcium ion channels play crucial roles in various biological functions and their dysfunction can lead to diseases. Traditional techniques have limitations in understanding the structure-function relationship of ion channels, which can be partially overcome by optogenetics. Optogenetics has significantly advanced our understanding of Ca2+ signaling proteins and their manipulation in biological processes.
Review
Biochemistry & Molecular Biology
Jiho Yoo
Summary: Mitochondria, organelles responsible for various cellular functions, uptake Ca2+ ions through the MCU holo-complex. The protein structure of the MCU holo-complex has recently been identified, providing insights into the uptake and regulation mechanisms.
Article
Cell Biology
Adela Tiffner, Lena Maltan, Marc Fahrner, Matthias Sallinger, Sarah Weiss, Herwig Grabmayr, Carmen Hoeglinger, Isabella Derler
Summary: This study reveals that non-conserved residues in TM3 control the maintenance of channel state and configuration, leading to varying degrees of gain- or loss-of-function in Orai1 and Orai3. Enhanced overall hydrophobicity in TM3 correlates with increased GoF mutant currents. While the overall activation mechanisms of Orai channels seem comparable, there are significant variations in key gating checkpoints crucial for pore opening.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Physiology
Ji-Hee Kim, Eun Young Park, Kyu-Hee Hwang, Kyu-Sang Park, Seong Jin Choi, Seung-Kuy Cha
Summary: Soluble alpha Klotho regulates store-operated Ca2+ entry (SOCE) by inhibiting PI3K-driven vesicular exocytosis of the Orai1 channel and contributes to the suppression of SOCE-mediated tumor cell migration.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yu-Ping Lin, Charmaine Nelson, Holger Kramer, Anant B. Parekh
Article
Multidisciplinary Sciences
Krishna Samanta, Gary R. Mirams, Anant B. Parekh
NATURE COMMUNICATIONS
(2018)
Article
Neurosciences
Krishna Samanta, Daniel Bakowski, Nader Amin, Anant B. Parekh
JOURNAL OF PHYSIOLOGY-LONDON
(2020)
Editorial Material
Cell Biology
Anant B. Parekh
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2019)
Article
Cell Biology
Pradeep Barak, Anant B. Parekh
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Yu-Ping Lin, Daniel Bakowski, Gary R. Mirams, Anant B. Parekh
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Yi-Chun Yeh, Yu-Ping Lin, Holger Kramer, Anant B. Parekh
HUMAN MOLECULAR GENETICS
(2020)
Review
Pharmacology & Pharmacy
Daniel Bakowski, Fraser Murray, Anant B. Parekh
Summary: CRAC channels are a major route for calcium entry in eukaryotic cells and have important implications in human diseases. Recent advances in understanding their structure have led to potential clinical applications, with CRAC channel blockers now entering clinical trials.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Article
Multidisciplinary Sciences
Pulak Kar, Yu-Ping Lin, Rajesh Bhardwaj, Charles J. Tucker, Gary S. Bird, Matthias A. Hediger, Carina Monico, Nader Amin, Anant B. Parekh
Summary: Eukaryotic cells confine second messengers to spatially restricted subcompartments to avoid conflicting outcomes. The smallest signaling unit, Ca2+ nanodomain, is formed when Ca2+ channels open. NFAT1 tethered to scaffolding protein AKAP79 is activated by local Ca2+ entry, providing a mechanism to selectively recruit a transcription factor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Adam G. Grieve, Yi-Chun Yeh, Yu-Fen Chang, Hsin-Yi Huang, Lucrezia Zarcone, Johannes Breuning, Nicholas Johnson, Kvido Strisovsky, Marion H. Brown, Anant B. Parekh, Matthew Freeman
Summary: Through the surveillance function of the rhomboid intramembrane protease RHBDL2, inappropriate activation of Orai1 and stochastic calcium signaling are prevented, leading to proper downstream effects related to T cell activation and cytokine expression. Loss of control of CRAC channel activity by RHBDL2 results in dysregulation of important biological processes, suggesting a potential ancient activity of rhomboid proteases in degrading unwanted signaling proteins.
Article
Biochemistry & Molecular Biology
Yu-Ping Lin, Erica Scappini, Carlos Landaverde, Frederick Parekh-Glitsch, Charles J. Tucker, Gary R. Mirams, Anant B. Parekh
Summary: AKAP79 is a critical protein that organizes calcium signaling at the plasma membrane and maintains long-term signal transduction. It interacts with Orai1 channels and activates calcium nanodomains to stimulate calcineurin. This study finds that the interaction between AKAP79 and Orai1 is transient, and the recycling of inactive NFAT1 to AKAP79 in the plasma membrane helps maintain signal coupling.
MOLECULAR AND CELLULAR BIOLOGY
(2022)
Article
Cell Biology
Pradeep Barak, Suneet Kaur, Erica Scappini, Charles J. Tucker, Anant B. Parekh
Summary: In many cell types, the rise in cytosolic Ca2+ due to opening of CRAC channels drives various cellular responses, but extended Ca2+ rise is toxic. This study reveals the role of PMCA4b in preventing prolonged cytosolic Ca2+ signal following CRAC channel activation and in maintaining Ca2+ nanodomains near the open channels, while protecting cells from Ca2+ overload.
Article
Cell Biology
Pulak Kar, Pradeep Barak, Anna Zerio, Yu-Ping Lin, Amy J. Parekh, Val J. Watts, Dermot M. F. Cooper, Manuela Zaccolo, Holger Kramer, Anant B. Parekh
Summary: The study explores the localization of signaling molecules in sub-cellular regions of eukaryotic cells, showing the presence of Ca2+ and cAMP signaling networks adjacent to Orai1 channels. Results indicate the absence of functional active Ca2+-activated adenylyl cyclases, including adenylyl cyclase 8, in HEK293 cells.
Review
Physiology
Pulak Kar, Krishna Samanta, Anant B. Parekh
CURRENT OPINION IN PHYSIOLOGY
(2020)
Meeting Abstract
Physiology
A. B. Parekh
Article
Cell Biology
Dominic Tscherrig, Rajesh Bhardwaj, Daniel Biner, Jan Dernic, Daniela Ross-Kaschitza, Christine Peinelt, Matthias A. Hediger, Martin Lochner
Summary: Changes in Ca2+ levels regulate many physiological functions, and the endoplasmic reticulum is the major Ca2+ store in cells. Store-operated calcium entry (SOCE) is a refilling process that involves protein-protein interactions between Ca2+ sensing STIM in the ER and Orai proteins in the plasma membrane, forming selective Ca2+ channels. Abnormal SOCE is associated with diseases and cancers, making STIM and Orai important therapeutic targets. Novel GSK-7975A-based molecular probes have been developed for studying SOCE in different cells and settings.
Article
Cell Biology
Nicola Fameli, Cornelis van Breemen, Klaus Groschner
Summary: The study provides evidence for the importance of junctional membrane architecture in cellular function. Through modeling and prediction, it is shown that nano-scale membrane spacing plays a crucial role in junctional ER Ca2+ refilling and signaling efficiency. Additionally, interactions between Ca2+ and the phospholipid membrane surface are suggested to support interfacial Ca2+ transport and receptor targeting. This research introduces a new concept in pathophysiology.
Article
Cell Biology
Satomi Ohtsuka, Yumi Miyai, Hiroyuki Mima, Masaki Magari, Yoichi Chiba, Futoshi Suizu, Hiroyuki Sakagami, Masaki Ueno, Hiroshi Tokumitsu
Summary: This study characterized the splice variants of mouse CaMKKI3/2 and found that CaMKKI3-3 and I3-3x were functionally active and likely to be bona fide CaMKIV kinases involved in the regulation of spermiogenesis.
