Article
Biochemistry & Molecular Biology
Ishika Basu, Hanjun Li, Andrew J. Trease, Paul L. Sorgen
Summary: T and B cell receptor signaling activates Akt, MAPKs, PKC, intracellular Ca2+, and calmodulin. This process involves Src and the phosphorylation of Cx43 residues Y247, Y265, and Y313 by BTK and ITK. Overexpression of BTK or ITK leads to increased Cx43 phosphorylation and decreased gap junction communication in HEK-293T cells. Activation of B cell receptor or T cell receptor enhances BTK and ITK activity, resulting in decreased Cx43 phosphorylation and altered gap junction function.
Article
Biochemistry & Molecular Biology
Ramona Matuseviciute, Egle Ignataviciute, Rokas Mickus, Sergio Bordel, Vytenis Arvydas Skeberdis, Vytautas Raskevicius
Summary: This study used molecular docking, QSAR, and 3D-QSAR to evaluate known Cx43 GJ inhibitors and identified a potential inhibitor - d-limonene. Experimental validation showed a good correlation between predicted and experimental inhibitory concentrations.
Article
Physiology
R. I. Jabr, S. C. Salvage, F. S. Hatch, C. H. Fry
Summary: Atrial fibrillation (AF) results from disordered atrial action potential conduction and reduced gap junction electrical conductance (G(j)). The calcineurin-dependent pathway involving protein phosphatase-1 (PP1) and phosphorylation of serine368 on connexin43 (pSer368-Cx43) is responsible for reducing G(j) in ventricular myocardium, but the corresponding pathways in left atrial myocardium, with a more complex connexin subtype profile, are still undefined. This study aims to characterize these pathways. The results show that low-Na solution reduces G(j) in guinea-pig left atrium, but this reduction is attenuated or prevented by calcineurin inhibitors cyclosporin-A or CAIP, respectively. Furthermore, the phosphorylation of Ser368-Cx43 in low-Na solution is also prevented by CAIP. Changes in Cx43/Cx40 phosphorylation status with raised intracellular [Ca2+](i) are mediated by calcineurin and PP2A-dependent pathways rather than PP1.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
Renju Pun, Michael H. H. Kim, Brian J. J. North
Summary: Intercellular communication in cardiomyocytes relies on Connexin 43 (Cx43) gap junction channels and hemichannels. The phosphorylation of Cx43 at Serine-368 (S368) by Protein Kinase C (PKC) isozymes affects the function and stability of Cx43, leading to altered intercellular communication. This review highlights the molecular and cellular mechanisms of PKC-mediated Cx43 phosphorylation and discusses its implications in various cardiac diseases, as well as the potential therapeutic targets.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Yuxing Li, Dilworth Y. Parkinson, Jun Feng, Chun-hong Xia, Xiaohua Gong
Summary: The study utilizes X-ray imaging to discover calcium precipitates in the lens cores of Cx46KO mice, indicating a new mechanism for age-related cataract formation.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Jing-Jun Zhao, Zheng-Hui Wang, Ying-Jie Zhang, Wen-Jing Wang, Ai-Fang Cheng, Pei-Jing Rong, Chun-Lei Shan
Summary: This study investigated the impact of auricular vagus nerve stimulation on the recovery of locomotor function in rats with cerebral ischemia/reperfusion injury. The findings suggested that the stimulation can promote recovery by altering the secretion of acetylcholine and inflammatory factors, as well as the phosphorylation of connexin 43.
NEURAL REGENERATION RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Scott D. Barnett, Hazik Asif, Mitchell Anderson, Iain L. O. Buxton
Summary: The currently available tocolytics are ineffective at significantly delaying preterm birth due to a lack of understanding of the mechanisms that drive spontaneous preterm labor (sPTL). However, this study has identified dysregulation of the contractile-associated protein connexin-43 (Cx43) in sPTL myometrium, and the pharmacological inhibition of Cx43 and its S-nitrosation with 18 beta-glycyrrhetinic acid and nebivolol provide a novel approach to significantly reduce contractions in human myometrial tissue. This new approach leverages maladjusted pathways in women who experience sPTL, offering potential for improved treatment strategies.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Multidisciplinary Sciences
William E. Myles, Sally A. McFadden
Summary: This study improved an existing method and developed two new approaches to assess electrical coupling between retinal neurons. Methods 2 and 3 showed more sensitivity and generalizability compared to Method 1, allowing for detailed evaluation and direct comparison between different cell networks.
Article
Cell Biology
Ladina Hosli, Noemi Binini, Kim David Ferrari, Laetitia Thieren, Zoe J. Looser, Marc Zuend, Henri S. Zanker, Stewart Berry, Martin Holub, Wiebke Mobius, Torben Ruhwedel, Klaus-Armin Nave, Christian Giaume, Bruno Weber, Aiman S. Saab
Summary: This study explores the role of astrocytes in modulating neural homeostasis, synaptic plasticity, and memory. By disrupting astrocytic gap junction coupling through knockout experiments, the researchers found that astrocytes play a vital role in maintaining neural excitability, synaptic transmission, and spatial cognition in the adult brain. These findings highlight the importance of astroglial networks in brain function.
Article
Biochemistry & Molecular Biology
Hye Kyeong Kwon, Hyunwoo Choi, Sung-Gyoo Park, Woo Jin Park, Do Han Kim, Zee-Yong Park
Summary: The study developed an integrated approach combining quantitative phosphoproteomics and cell-based functional screening to identify functionally important phosphorylation sites among differentially phosphorylated proteins in cardiac hypertrophy. The approach was able to validate the inhibitory effects on cardiac hypertrophic growth of specific phosphorylation sites in NRVMs, demonstrating its potential for large-scale and high-throughput analyses.
MOLECULES AND CELLS
(2021)
Review
Biochemistry & Molecular Biology
Jose F. Ek-Vitorin, Jean X. Jiang
Summary: This article reviews the literature on lens connexin mutations and other factors associated with cataract development, highlighting the role of connexin channel dysfunction and protein damage accumulation in cataract development. Phosphorylation improves the permeability of connexin channels and helps maintain lens transparency.
Article
Biochemical Research Methods
Richard Y-C Huang, Yun Wang, Amy D. Jhatakia, Andy X. Deng, Christine Bee, Shrikant Deshpande, Vangipuram S. Rangan, Natalie Bezman, Olafur Gudmundsson, Guodong Chen
Summary: NKG2A, an immune checkpoint inhibitor, forms a heterodimer with CD94 and recognizes HLA-E antigen. Mass spectrometry techniques can provide insights into the structure of NKG2A/CD94 heterodimer and the mechanisms of antibody interactions with it.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Review
Anatomy & Morphology
Stephan Maxeiner, Selina Gebhardt, Frederick Schweizer, Agnes E. Venghaus, Gabriela Krasteva-Christ
Summary: This article discusses the differences between the human genome and the mouse genome, particularly the issues in generating gene research models, pointing out the absence of some genes in mice and rats.
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER
(2021)
Article
Chemistry, Multidisciplinary
Beryl X. Li, Daniel K. Kim, Steven Bloom, Richard Y. -C. Huang, Jennifer X. Qiao, William R. Ewing, Daniel G. Oblinsky, Gregory D. Scholes, David W. C. MacMillan
Summary: This study presents a novel method for site-selective tyrosine bioconjugation using photoredox catalysis, which allows for chemically modifying native proteins with high site-selectivity. The water-soluble photocatalyst lumiflavin has been demonstrated to induce oxidative coupling between a phenoxazine dialdehyde tag and a single tyrosine site on native proteins, even in the presence of multiple tyrosyl side chains, enabling the synthesis of structurally defined fluorescent conjugates.
Article
Multidisciplinary Sciences
Gustavo Fenalti, Nicolas Villanueva, Mark Griffith, Barbra Pagarigan, Sirish Kaushik Lakkaraju, Richard Y-C Huang, Nadia Ladygina, Alok Sharma, David Mikolon, Mahan Abbasian, Jeffrey Johnson, Haralambos Hadjivassiliou, Dan Zhu, Philip P. Chamberlain, Ho Cho, Kandasamy Hariharan
Summary: CD47 is the only 5-TM spanning receptor of the immune system, with its ECD serving as a cell surface marker of self that binds SIRP alpha and inhibits macrophage phagocytosis. The crystal structure of CD47 bound to the function-blocking antibody B6H12 provides insights into its molecular mechanism.
NATURE COMMUNICATIONS
(2021)
Correction
Biochemistry & Molecular Biology
Sean M. Gettings, Stephan Maxeiner, Maria Tzika, Matthew R. D. Cobain, Irina Ruf, Fritz Benseler, Nils Brose, Gabriela Krasteva-Christ, Greetje Vande Velde, Matthias Schonberger, Mike Althaus
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Neurosciences
Soni Shankhwar, Karin Schwarz, Rashmi Katiyar, Martin Jung, Stephan Maxeiner, Thomas C. Suedhof, Frank Schmitz
Summary: In this study, we investigated the essential role of the RIBEYE B-domain in the assembly of synaptic ribbons. Our results demonstrate that the B-domain is necessary for the assembly of RIBEYE into synaptic ribbons, providing further evidence that RIBEYE is the central organizer of these structures.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Bjorn-Hendrik Peters, James Bautista, Thomas R. Slaney, Hongyue Guo, Richard Y-C Huang, Mary E. Krause, Ming Zeng, Julie Cheng, Zhi Chen
Summary: Antibody-based therapeutic proteins have complex structures with charge variants, and accurate analysis of these variants is important for manufacturing process consistency and protein stability. By optimizing the iCIEF master mix buffer and removing sialic acid, the challenge of monitoring stability for a highly sialylated bispecific antibody was overcome. The method was validated for linearity, precision, LOD, LOQ, accuracy, and robustness, and correlated with LC-MS tryptic peptide mapping results.
Review
Chemistry, Analytical
Xiaoran Roger Liu, Richard Y-C Huang, Feifei Zhao, Guodong Chen, Li Tao
Summary: This article discusses the application of mass spectrometry (MS) technology in epitope mapping of protein therapeutics. Through reversible and irreversible labeling methods such as hydrogen/deuterium exchange, the changes in solvent accessibilities during binding interactions can be assessed. These methods have been widely used in characterizing the binding interface within immunocomplexes.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Multidisciplinary Sciences
Julie A. Zorn, Matthew L. Wheeler, Ralston M. Barnes, Jim Kaberna, Winse Morishige, Marek Harris, Richard Y-C Huang, Jack Lohre, Yu Ching Chang, Bryant Chau, Kathleen Powers, Ian Schindler, Naveen Neradugomma, Winston Thomas, Xiaoyun Liao, Yinhan Zhou, Sean M. West, Feng Wang, Srikanth Kotapati, Guodong Chen, Sayumi Yamazoe, Anastasia Kosenko, Gavin Dollinger, Tim Sproul, Arvind Rajpal, Pavel Strop
Summary: T-cell engagers (TCEs) are a class of biotherapeutics that are being studied in clinical trials for the treatment of various blood and solid tumor cancers. Researchers have developed a mouse model that allows for the evaluation of the efficacy of TCEs in hosts with intact immune systems. This model demonstrates that TCEs can effectively induce T-cell killing of target cells and sustain depletion of peripheral B cells, making it a valuable tool for studying the in vivo efficacy of TCEs.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Stephan Maxeiner, Fritz Benseler, Nils Brose, Gabriela Krasteva-Christ
Summary: The neuroligin-4 protein has long puzzled scientists due to its association with autism spectrum disorders. Recently, it was discovered that there are significant differences in the neuroligin-4 sequence between humans and mice, which can be explained by changes in the pseudoautosomal region of sex chromosomes. This study found sex chromosome-specific copies of neuroligin-4 genes in gerbils, marking the first time this has been observed in rodents. Furthermore, it was shown that neuroligin-4 diversification in sex chromosome-specific copies has occurred multiple times independently during mammal evolution, challenging the notion of a single common ancestor for Y-chromosomal NLGN4Y genes.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Editorial Material
Anatomy & Morphology
Stephan Maxeiner, Thomas Tschernig, Erich Brenner
ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER
(2022)
Article
Biochemistry & Molecular Biology
Shweta Suiwal, Mayur Dembla, Karin Schwarz, Rashmi Katiyar, Martin Jung, Yvonne Carius, Stephan Maxeiner, Marcel A. Lauterbach, C. Roy D. Lancaster, Frank Schmitz
Summary: Unc119 protein mediates transport of myristoylated proteins to the photoreceptor outer segment and is also enriched in photoreceptor synapses. The synaptic ribbon could be involved in the discharge of Unc119-bound lipid-modified proteins. Proteins associated with Unc119 may play important roles in photoreceptor synapses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Monika Hollenhorst, Praveen Kumar, Maxim Zimmer, Alaa Salah, Stephan Maxeiner, Mohamed Ibrahem Elhawy, Saskia B. Evers, Veit Flockerzi, Thomas Gudermann, Vladimir Chubanov, Ulrich Boehm, Gabriela Krasteva-Christ
Summary: This study found that brush cells play a regulatory role in mucociliary clearance in the airways. Activation of brush cells leads to the inhibition of epithelial sodium channels through the bitter taste signaling cascade, resulting in a reduction of mucociliary clearance.
Review
Neurosciences
Stephan Maxeiner, Gabriela Krasteva-Christ, Mike Althaus
Summary: Synthesis of DNA fragments based on gene sequences from public resources has replaced traditional cloning methods. However, errors in database entries can lead to false sequence information and impact protein characterization in expression systems. Five common problems in public resources: incomplete gene annotation, incorrect annotations, automated corrections in transcripts, sequence mismatches, and lack of experimental validation for splicing patterns. This review presents a strategy to bypass these issues and avoid critical mistakes in future studies.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Biochemistry & Molecular Biology
Jong Hee Song, Nicole D. Wagner, Jing Yan, Jing Li, Richard Y-C Huang, Aaron J. Balog, John A. Newitt, Guodong Chen, Michael L. Gross
Summary: By using charge reduction, native mass spectrometry, and gas-phase activation methods, we demonstrated an integrated approach for in-depth analysis of PROTAC-linked ternary complexes. This approach may help in screening for ternary complex formation and PROTAC-protein contacts, potentially reporting on PROTAC-induced protein-protein interactions known to be correlated with PROTAC selectivity and efficacy.
CELL CHEMICAL BIOLOGY
(2021)