Article
Multidisciplinary Sciences
Ninghai Gan, Yan Han, Weizhong Zeng, Yan Wang, Jing Xue, Youxing Jiang
Summary: TRPML1 is a Ca2+-permeable, nonselective cation channel expressed in endolysosomes, which is activated by cooperation between PI(3,5)P2 and rapamycin. The cryoEM structures and electrophysiology studies provide insights into the activation mechanism of TRPML1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Maike R. Pollmanns, Judith Beer, Ines Rosignol, Natalia Rodriguez-Muela, Bjoern H. Falkenburger, Elisabeth Dinter
Summary: This study demonstrated that activating TRPML1 facilitates the clearance of alpha-synuclein aggregates by promoting autophagosome maturation. These findings suggest that targeting TRPML1 may be a potential therapeutic strategy for Parkinson's disease, which should be further validated in animal models of alpha-synuclein pathology.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Edwin C. Fluck, Aysenur Torun Yazici, Tibor Rohacs, Vera Y. Moiseenkova-Bell
Summary: Transient receptor potential vanilloid 5 (TRPV5) is a calcium-selective ion channel that plays a crucial role in maintaining calcium homeostasis in the kidney. This study investigates the regulation of TRPV5 by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) and calmodulin (CaM), as well as the effects of parathyroid hormone (PTH), metabolic acidosis, and protein kinase A (PKA) on TRPV5 activity. The findings reveal that low pH inhibits TRPV5 by preventing PI(4,5)P-2 activation, and PKA controls TRPV5 activity by preventing CaM binding and channel inactivation.
Article
Biochemistry & Molecular Biology
Guangbi Li, Dandan Huang, Ningjun Li, Joseph K. Ritter, Pin-Lan Li
Summary: The study found that ROS levels increased in podocytes after Hcy stimulation, leading to activation of NLRP3 inflammasomes and the presence of inflammatory cytokines in MVBs. Inhibiting NADPH oxidase and using ROS scavengers prevented these effects.
Review
Immunology
Abeer F. Alharbi, John Parrington
Summary: Recent years have seen a growing interest in the role of endolysosomal Ca2+ signalling in immunity, particularly the contribution of channels such as TPCs, TRPMLs, and P2X4R in immune cell function and immune responses. Despite the lack of clinical studies, emerging biomedical data has provided valuable insights into the importance of these channels in immune processes. Further investigations are needed to fully understand the immunological significance of endolysosomal Ca2+ signalling and its potential as biomarkers and therapeutic targets in immune-related diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Yang Li, Xue Yang, Yuequan Shen
Summary: Orai channels, belonging to the CRAC channel family, play a crucial role in Ca2+ influx triggered by ER Ca2+ depletion. While structural and functional studies have advanced our understanding of Orai channel activation, the gating mechanism for Ca2+ permeation remains less well understood. This review summarizes existing structural studies, detailing features, comparing closed and open states, and proposing a push-pull model for Ca2+ permeation.
Review
Cell Biology
Gerald Thiel, Tobias Schmidt, Oliver G. Roessler
Summary: Ca2+ ions act as second messengers in the regulation of various cellular events, with a non-uniform distribution within the cytoplasm. Elevated Ca2+ concentration changes the genetic expression pattern of the cell by activating different transcription factors. The mode of Ca2+ entry and the role of enzymes as signal transducers play important roles in gene transcription regulation.
Article
Multidisciplinary Sciences
Thamali Ayagama, Samuel J. Bose, Rebecca A. Capel, David A. Priestman, Georgina Berridge, Roman Fischer, Antony Galione, Frances M. Platt, Holger Kramer, Rebecca A. B. Burton
Summary: A label-free proteomics method suitable for small cardiac tissue biopsies was described in this study, allowing for the study of endolysosomal proteins. The analysis of density-separated fractions revealed good coverage of RAB proteins and lysosomal cathepsins in the purified endolysosomal fraction, including cardiac-specific cathepsin D.
Article
Biology
Kangcheng Song, Miao Wei, Wenjun Guo, Li Quan, Yunlu Kang, Jing-Xiang Wu, Lei Chen
Summary: TRPC5 channel is a nonselective cation channel involved in various physiological processes. Inhibitors of TRPC5, such as clemizole and HC-070, stabilize the ion channel in a nonconductive closed state, potentially offering new therapeutic strategies for anxiety disorders, depression, and kidney diseases. The cryo-EM structures of human TRPC5 with inhibitors provide insights into the binding sites and inhibitory mechanisms, facilitating the development of more effective inhibitors targeting TRPC5.
Review
Multidisciplinary Sciences
Wenping Wu, Jimin Zheng, Zongchao Jia
Summary: The mitochondrial uniporter is a Ca2+-selective ion-conducting channel in the inner mitochondrial membrane composed of MCU, MCUb, EMRE, MICU1, and MICU2. Recent structural studies have provided insights into the component structures and their spatial relationship, contributing to a better understanding of mitochondrial Ca2+ uptake and regulation. Further research in this area could lead to advancements in studying mitochondrial Ca2+ permeation and related diseases.
Review
Biochemistry & Molecular Biology
Cheng-Chang Chen, Einar Krogsaeter, Christian Grimm
Summary: TPCs and TRPML2 play crucial roles in regulating and detecting changes in surface-to-volume ratio of endolysosomes, promoting endocytic and recycling traffic. They are highly expressed in macrophages and contribute to immune cell function.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Sudarshi Premawardhana Dassanayake Mudiyanselage, Matthew J. Gage
Summary: The study reveals the importance of PPAK and poly-E motifs in the elastic properties of the PEVK region. It shows that poly-E motifs are sensitive to pH changes and that the length of poly-E motifs and the presence of PPAK motifs affect this sensitivity. Additionally, calcium binding increases the conformational flexibility of the poly-E motifs, which is blocked by PPAK motifs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Arthur Neuberger, Kirill D. Nadezhdin, Alexander I. Sobolevsky
Summary: TRPV6 is a calcium-selective ion channel with potential as a drug target. The study presents cryo-EM structures of TRPV6 with inhibitors ruthenium red and econazole, revealing their mechanisms of inhibition. Both inhibitors induce conformational changes in TRPV6, guiding the design of new inhibitors.
NATURE COMMUNICATIONS
(2021)
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
Immunology
Yuanyuan Duan, Guangqiang Li, Miaomiao Xu, Xiaofei Qi, Mingxia Deng, Xuejia Lin, Zhiwei Lei, Yi Hu, Zhenghu Jia, Quanli Yang, Guangchao Cao, Zonghua Liu, Qiong Wen, Zhenhua Li, Jie Tang, Wei Kevin Zhang, Pingbo Huang, Limin Zheng, Richard A. Flavell, Jianlei Hao, Zhinan Yin
Summary: CFTR, a chloride and ion channel regulator, plays a role in regulating IFN-γ production and antitumor activity of gamma delta T cells. Mechanisms involve TCR-dependent and Ca2+ influx pathways. Modifying CFTR activity in gamma delta T cells could be a potential immunotherapeutic strategy for cancer.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Microbiology
Bret N. Peterson, Megan K. M. Young, Shukun Luo, Jeffrey Wang, Aaron T. Whiteley, Joshua J. Woodward, Liang Tong, Jue D. Wang, Daniel A. Portnoy
Article
Biochemistry & Molecular Biology
Liang Tong
Summary: SARM1 protein acts as an executioner of axon degeneration through its NAD(+) hydrolase activity. Studies have shown that it is activated at lower NAD(+) levels and causes NAD(+) collapse and axon degeneration.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Bibhuti Ranjan, Philip H. Choi, Santhosh Pillai, Kugenthiren Permaul, Liang Tong, Suren Singh
Summary: The cyanase from Thermomyces lanuginosus has the highest catalytic efficiency among these enzymes, and its crystal structure study provides insights into both catalytic mechanism and inhibition, with potential applications in biotechnological fields.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Shukun Luo, Bruna G. Coutinho, Prikshat Dadhwal, Yasuhiro Oda, Jiahong Ren, Amy L. Schaefer, E. Peter Greenberg, Caroline S. Harwood, Liang Tong
Summary: Some plant-associated proteobacteria have LuxR family transcription factors known as PipR subfamily members that play important roles in interactions with plant hosts and bacterial virulence of plants. The ethanolamine derivative, HEHEAA, was identified as an effective effector of PipR-mediated gene regulation in the plant endophyte Pseudomonas GM79. Crystallization of a HEHEAA-responsive SBP revealed the molecular basis of PipR system responses to plant factors, showing that different PipR-associated SBPs bind different effectors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Chun-Min Shan, Jin-Kwang Kim, Jiyong Wang, Kehan Bao, Yadong Sun, Huijie Chen, Jia-Xing Yue, Alessandro Stirpe, Zhiguo Zhang, Chao Lu, Thomas Schalch, Gianni Liti, Peter L. Nagy, Liang Tong, Feng Qiao, Songtao Jia
Summary: This study reveals that in fission yeast, nuclei containing H3K9M are widely distributed across the genome, but the histone H3K9 methyltransferase Clr4 is mainly sequestered at pericentric repeats. This selective sequestration of Clr4 depends on both H3K9M and H3K14 ubiquitylation, which synergize to inhibit Clr4 enzymatic activity.
Review
Biochemistry & Molecular Biology
Zbigniew Dominski, Liang Tong
Summary: Replication-dependent histone mRNAs in animal cells have a unique 3' end structure, distinct from other eukaryotic mRNAs. The U7 snRNP plays a key role and shares some proteins with the canonical cleavage and polyadenylation machinery.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Microbiology
Alex J. Pollock, Philip H. Choi, Shivam A. Zaver, Liang Tong, Joshua J. Woodward
Summary: c-di-AMP is a crucial nucleotide second messenger in bacteria, regulating various cellular processes. The development of a novel biosensor, CDA5, enables the detection of c-di-AMP dynamics within bacterial populations at single-cell resolution, providing valuable insights into its regulation.
JOURNAL OF BACTERIOLOGY
(2021)
Correction
Biochemistry & Molecular Biology
Selom K. Doamekpor, Agnieszka Gozdek, Aleksandra Kwasnik, Joanna Kufel, Liang Tong
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Pedro A. Gutierrez, Kirk Baughman, Yadong Sun, Liang Tong
Summary: CPSF73 is an endonuclease that catalyzes the cleavage reaction for 3'-end processing of mRNA precursors in two distinct machineries. Recent studies suggest that CPSF73 is a potential target for developing anticancer, antimalarial, and antiprotozoal drugs. By developing a real-time fluorescence assay, the nuclease activity of CPSF73 can be efficiently measured.
Article
Biology
Xiangdong Zheng, Huan Li, Zhengshan Hu, Deyuan Su, Jian Yang
Summary: This study investigates the pathogenic mechanisms of the R410W mutation in the human CNGA3 channel associated with achromatopsia. The mutation leads to spontaneous channel opening and cell death, providing insights into the role of CNG channels in cone degeneration and suggesting potential mutation-specific treatments for retinopathy.
COMMUNICATIONS BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Deyuan Su, Ye Gong, Songyu Li, Jian Yang, Yin Nian
Summary: The study reveals the strong analgesic effects of Cyclovirobuxine D, mainly through blockade of the Ca(v)3.2 channel, providing a compelling rationale and foundation for repurposing Cyclovirobuxine D in pain management.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
John H. Van Drie, Liang Tong
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Cell Biology
Keith Hamilton, Liang Tong
GENES & DEVELOPMENT
(2020)
Review
Biochemistry & Molecular Biology
Yadong Sun, Keith Hamilton, Liang Tong
TRANSCRIPTION-AUSTIN
(2020)