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
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)
Review
Biochemistry & Molecular Biology
Adela Tiffner, Lena Maltan, Sarah Weiss, Isabella Derler
Summary: This article discusses the highly coordinated and precise regulation of basal cytosolic Ca2+ concentrations required for cell survival and normal cell function, emphasizing the role of the Ca2+ release-activated Ca2+ (CRAC) channel in facilitating Ca2+ entry into cells. It also analyzes the structure and function of the Orai1 channel, as well as the impact of various Orai1 mutations on channel opening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Joel Nieto-Felipe, Jose Sanchez-Collado, Isaac Jardin, Gines M. Salido, Jose J. Lopez, Juan A. Rosado
Summary: Store-operated Ca2+ entry is a widely observed mechanism in mammalian cells that regulates various physiological processes. The study reveals that Orai1 alpha, not Orai1 beta, plays a significant role in agonist-induced NF-kappa B transcriptional activity, which is dependent on Ca2+ influx and involves PKC beta activation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Editorial Material
Cell Biology
Raz Palty
Summary: Loss-of-function mutations in the regulatory component CRACR2A of the CRAC channel may contribute to late onset immunodeficiency.
Editorial Material
Cell Biology
Sonal Srikanth, Yousang Gwack
Summary: Researchers have successfully developed a novel light-operated Ca2+ channel that can selectively and efficiently elevate cytoplasmic Ca2+ levels.
Editorial Material
Cell Biology
Daniel Bonhenry, Romana Schober, Rainer Schindl
Summary: The store-operated calcium channels Orai13 have extraordinary long and funnel-like pores, with a hydrophobic segment centrally located in the Orai pore controlling gating. A recent study has described decisive binding between three residues that control the open and closed conformation of Orai channels.
Article
Biochemistry & Molecular Biology
Tomoya Uchimura, Hidetoshi Sakurai
Summary: The study showed that STIM1-Orai1 is a molecular target of store-operated Ca2+ channels (SOCs) and modulating its activity effectively ameliorated the decline in contractile performance in DMD.SOCs play a major role in causing dystrophin deficiency-dependent Ca2+ overload, and targeting STIM1-Orai1-mediated Ca2+ overload is an effective approach to rescuing contractile phenotypes in DMD.
Article
Respiratory System
Alexandra S. Goriounova, Rodney C. Gilmore, Joe A. Wrennall, Robert Tarran
Summary: This study found that Orai1 is more active in asthma and CF than in normal lungs, indicating that it is a relevant target for reducing pulmonary inflammation.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Chemistry, Medicinal
Yu-Shiuan Wang, Teng-Kuang Yeh, Wei-Chiao Chang, Jing-Ping Liou, Yi-Min Liu, Wan-Chen Huang
Summary: Ca2+ entry from store-operated Ca2+ channel (SOC) is involved in regulating colorectal cancer progression. In this study, compound 2,6-Difluoro-N-(5-(4-fluorophenyl)pyridine-2-yl)benzamide (MPT0M004, 8a) demonstrated prominent inhibitory ability on SOC and lower cytotoxicity compared to 2-APB. It has the potential to be developed into a drug for treating colorectal cancer.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Lena Maltan, Ana-Marija Andova, Isabella Derler
Summary: The composition and dynamics of the lipid membrane play a crucial role in determining the physical properties of the bilayer and affecting the function of membrane transporters. The review focuses on the Ca2+ release-activated Ca2+ ion channel (CRAC), which is activated by changes in the intracellular Ca2+ concentration. The activation and deactivation of the CRAC channel are fine-tuned by lipids and accessory proteins.
Article
Cell Biology
Jesse Gammons, Janith Halpage, Salvatore Mancarella
Summary: The study utilized the BioID technique to investigate the STIM1 interactome and identified Gelsolin (GSN) as a new member involved in cytoskeletal remodeling. Validation in mouse embryonic fibroblast cell lines and neonatal cardiomyocytes highlighted the crucial role of STIM1/GSN in the structure and function of the cytoskeleton.
Article
Biochemical Research Methods
Noemi Renaudin, Charlie Demene, Alexandre Dizeux, Nathalie Ialy-Radio, Sophie Pezet, Mickael Tanter
Summary: Ultrasound localization microscopy (ULM) is a technique that allows localization and monitoring of cerebral blood flow at a small scale. By detecting the flow of injected microbubbles, ULM provides real-time information about brain activity at high spatiotemporal resolution.
Article
Medicine, General & Internal
Chih-Chin Kao, Henry Sung-Ching Wong, Yu-Jia Wang, Wan-Hsuan Chou, Dyah Aryani Perwitasari, Mai-Szu Wu, Wei-Chiao Chang
Summary: The genetic polymorphisms of STIM1 and ORAI1 are significantly associated with erythropoietin resistance in patients with renal failure. Specifically, the AA genotype of rs1561876 in STIM1 and the CC or CT genotypes of rs6486795 in ORAI1 were found to be linked to increased risk of erythropoietin resistance. Functional annotation revealed differences in gene expression levels related to calcium signaling, highlighting its importance in erythropoietin resistance.
Editorial Material
Cell Biology
Murali Prakriya, Priscilla See-Wai Yeung, Megumi Yamashita
Summary: Store-operated Orai channels play a crucial role in mobilizing Ca2+ signals in cells. Understanding the structure of open channels is vital for unraveling the mechanism of channel activation. A new study discussed in the article brings us closer to understanding the molecular basis of Orai channel activation through unveiling the structure of a constitutively active Orai mutant.