Article
Biochemistry & Molecular Biology
Abigail Taylor, Mark Warner, Christopher Mendoza, Calvin Memmott, Tom LeCheminant, Sara Bailey, Colter Christensen, Julie Keller, Arminda Suli, Dario Mizrachi
Summary: The tight junction (TJ) is a structure composed of multiple proteins responsible for cell-cell adhesion in polarized endothelium and epithelium. This article introduces a new experimental method to study the membrane protein claudins (CLDNs), providing a novel approach for studying other membrane proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Alex J. Vecchio, Sewwandi S. Rathnayake, Robert M. Stroud
Summary: The study reveals the molecular and structural basis of how CpE targets susceptible claudins, as well as differences in the primary CpE receptors in mice and humans due to sequence changes in the target motif.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Kenta Shigetomi, Yumiko Ono, Kenji Matsuzawa, Junichi Ikenouchi
Summary: It has been found that cholesterol accumulation is essential for the formation of tight junctions, which are crucial for the epithelial barrier. Despite the absence of tight junctions, cholesterol still accumulates normally in the vicinity of the apical junctions. Moreover, a claudin mutant that cannot bind to Zonula Occludens (ZO) proteins can still form tight junction strands. ZO proteins are not only scaffolds for claudins, but also promote the formation of cholesterol-rich membrane domains at apical junctions through their effect on the junctional actomyosin cytoskeleton.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Rina Fujiwara-Tani, Shiori Mori, Ruiko Ogata, Rika Sasaki, Ayaka Ikemoto, Shingo Kishi, Masuo Kondoh, Hiroki Kuniyasu
Summary: CLDN4 is a crucial component of tight junctions in epithelial cells and is overexpressed in many epithelial malignancies. Changes in CLDN4 expression are associated with epigenetic factors, inflammation, and growth factor signaling. CLDN4 plays a role in maintaining the tumor microenvironment and acts as a barrier to anticancer drug entry.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Food Science & Technology
Yunika Mayangsari, Mayu Okudaira, Chinatsu Mano, Yuki Tanaka, Osamu Ueda, Tomohiro Sakuta, Yoshiharu Suzuki, Yoshinari Yamamoto, Takuya Suzuki
Summary: Research showed that DMF can enhance intestinal TJ barrier integrity by increasing the expression of occludin and claudin-1, while reducing the expression of claudin-2. This regulation involves the induction of occludin protein translation via mTOR and silencing Cldn2 mRNA via miR-16-5p.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Biochemistry & Molecular Biology
Lena Ahlswede, Carmen Siebenaller, Benedikt Junglas, Nadja Hellmann, Dirk Schneider
Summary: Human Claudin-7 (Cldn7) plays a role in tight junction formation between cells. This study focuses on the in vitro analysis of Cldn7 through heterologous expression and purification in E. coli. The study reveals the existence of monomeric, hexameric, and higher oligomeric forms of Cldn7, and identifies two amino acids that mediate electrostatic cis-interactions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Fumisato Maesaka, Masaomi Kuwada, Shohei Horii, Shingo Kishi, Rina Fujiwara-Tani, Shiori Mori, Kiyomu Fujii, Takuya Mori, Hitoshi Ohmori, Takuya Owari, Makito Miyake, Yasushi Nakai, Nobumichi Tanaka, Ujjal Kumar Bhawal, Yi Luo, Masuo Kondoh, Kiyohide Fujimoto, Hiroki Kuniyasu
Summary: In bladder urothelial carcinoma (BUC), the overexpression of CLDN4 is associated with cancer progression. Through analyzing BUC cases, it was found that hypomethylation of CLDN4 promoter DNA increases CLDN4 expression and promotes cell proliferation, stemness, and epithelial-mesenchymal transition. Treatment with demethylating agent AZA leads to excessive CLDN4 expression, specifically the TJ-unintegrated CLDN4 monomer. The TJ-unintegrated CLDN4 binds to integrin beta 1 and enhances stemness, drug resistance, and metastatic ability of the cells, as well as exhibits an anti-apoptosis effect via FAK phosphorylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Environmental Sciences
Roziana Kamaludin, Zatilfarihiah Rasdi, Mohd Hafiz Dzarfan Othman, Siti Hamimah Sheikh Abdul Kadir, Mohd Yusri Idorus, Jesmine Khan, Wan Nor I'zzah Wan Mohamad Zain, Ahmad Fauzi Ismail, Mukhlis A. Rahman, Juhana Jaafar
Summary: This study found that BPA exposure can affect the small intestine and intestinal barrier of pregnant rats and their fetuses, but BPA-treated water through photocatalytic membrane does not have detrimental effects on the gastrointestinal tract.
Article
Cell Biology
Hyunjhung Jhun, Won-Young Lee, Jin-Ki Park, Sun-Goo Hwang, Hyun-Jung Park
Summary: Cryptorchidism may affect Claudin expression, which in turn impacts the proliferation of Sertoli cells and spermatogenesis.
Article
Medicine, Research & Experimental
Harleen Kaur, Regis Moreau
Summary: The role of mTORC1 in the regulation of intestinal barrier function and permeability remains to be fully elucidated.
Article
Multidisciplinary Sciences
Caroline Hempel, Rita Rosenthal, Anja Fromm, Susanne M. Krug, Michael Fromm, Dorothee Gunzel, Joerg Piontek
Summary: This study analyzed the structural and functional differences between claudin-15 and claudin-10b cation channels and identified several mutants that affect ion permeability and pore diameter. Furthermore, the study revealed that the charge at the W63/K64 position has an impact on the assembly and properties of claudin-10b channels but not claudin-15 channels.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Review
Multidisciplinary Sciences
Erika Wakayama, Taiki Kuzu, Keisuke Tachibana, Ryuichi Hirayama, Yoshiaki Okada, Masuo Kondoh
Summary: The blood-brain barrier poses a challenge to drug delivery to the central nervous system. Among the components of the tight junctions in the blood-brain barrier, claudin-5 has been studied extensively as a target for enhancing drug permeation into the brain. However, sustained knockdown of claudin-5 is lethal in mice and administration of an anti-claudin-5 antibody can cause convulsions in nonhuman primates.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Agriculture, Multidisciplinary
Dina Mustika Rini, Yusuke Nakamichi, Tomotake Morita, Hiroyuki Inoue, Yoichi Mizukami, Yoshinari Yamamoto, Takuya Suzuki
Summary: This study revealed that xylobiose suppresses Claudin 2 expression and increases HSP27 expression in intestinal Caco-2 cells via post-transcriptional regulation, potentially strengthening intestinal barrier integrity. However, these effects seem to occur via different signaling pathways. Our findings may help to assess the physiological role of xylobiose.
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
(2023)
Article
Physiology
Dorothee Guenzel
Summary: The concept of solvent drag involves the frictional coupling between water and solutes in the same pore for transport. It has been applied to transport processes across cell membranes and along the paracellular pathway. Water-driven solute transport has been proposed as the major mechanism for absorption in the small intestine and reabsorption in the renal proximal tubule. However, the discovery of aquaporins and the claudin protein family has led to a reassessment of the solvent drag concept for transepithelial water and solute transport.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Reproductive Biology
Susanne C. Grund, Xin Xin Wu, Dominik Mueller, Gunther Wennemuth, Ruth Gruemmer
Summary: Deletion of claudin-3 in the endometrium impairs decidualization and leads to reduced size of implantation sites and fetal weight. Transcription downregulation of various decidua-associated genes may contribute to the impairment of decidualization.
BIOLOGY OF REPRODUCTION
(2022)
Article
Urology & Nephrology
Tilman Breiderhoff, Nina Himmerkus, Luca Meoli, Anja Fromm, Sebastian Sewerin, Natalia Kriuchkova, Oliver Nagel, Yury Ladilov, Susanne M. Krug, Catarina Quintanova, Meike Stumpp, Dieter Garbe-Schoenberg, Ulrike Westernstroeer, Cosima Merkel, Merle Annette Brinkhus, Janine Altmuller, Michal R. Schweiger, Dominik Muller, Kerim Mutig, Markus Morawski, Jan Halbritter, Susanne Milatz, Markus Bleich, Dorothee Guenzel
Summary: Recent study indicates that claudin-10a is the major paracellular anion channel in the proximal tubule, and its deficiency leads to excessive reabsorption of calcium and magnesium. Various analyses, including electrophysiological studies, suggest compensatory transcellular transport in proximal and distal tubule segments, as well as metabolic adaptation in the proximal tubule, to counterbalance the loss of paracellular anion permeability.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Caroline Hempel, Rita Rosenthal, Anja Fromm, Susanne M. Krug, Michael Fromm, Dorothee Gunzel, Joerg Piontek
Summary: This study analyzed the structural and functional differences between claudin-15 and claudin-10b cation channels and identified several mutants that affect ion permeability and pore diameter. Furthermore, the study revealed that the charge at the W63/K64 position has an impact on the assembly and properties of claudin-10b channels but not claudin-15 channels.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Multidisciplinary Sciences
Alexander Belyy, Florian Lindemann, Daniel Roderer, Johanna Funk, Benjamin Bardiaux, Jonas Protze, Peter Bieling, Hartmut Oschkinat, Stefan Raunser
Summary: This study reveals in atomic detail how the TccC3 enzyme modifies actin and disrupts the cellular cytoskeleton. The binding of TccC3 to F-actin occurs through an induced-fit mechanism, leading to the transfer of ADP-ribose to a specific site on F-actin. This site-specific modification prevents the interaction of F-actin with depolymerization factors, impairing actin network turnover and promoting steady actin polymerization.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
S. M. Ayala Mariscal, M. L. Pigazzini, Y. Richter, M. Ozel, I. L. Grothaus, J. Protze, K. Ziege, M. Kulke, M. ElBediwi, J. V. Vermaas, L. Colombi Ciacchi, S. Koppen, F. Liu, J. Kirstein
Summary: Huntington's disease is a neurodegenerative disorder caused by aggregation-prone mutant HTT protein. The trimeric chaperone complex formed by Hsc70, DNAJB1, and Apg2 can suppress and reverse the aggregation of HTTExon1Q(48) by binding to the HTT protein's poly-proline region through DNAJB1. The mutation of the conserved H244 in DNAJB1's HBM specifically affects the suppression and disaggregation of HTT fibrils, highlighting the importance of this interaction site for Huntington's disease.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Yiyu Wang, Joerg Scheffel, Carolina Ayala Vera, Wei Liu, Dorothee Guenzel, Dorothea Terhorst-Molawi, Marcus Maurer, Sabine Altrichter
Summary: This study aimed to assess the rate and extent of impaired sweating in patients with cholinergic urticaria (CholU) and its association with disease duration and severity. The results showed that reduced sweating is common in CholU patients, especially in those with long-standing and severe disease. The reduced expression of CHRM3 and ACh-E may be responsible for the impaired sweating in these patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Laura-Sophie Beier, Ayk Waldow, Saeed Khomeijani Farahani, Roman Mannweiler, Sabine Vidal-Y-Sy, Johanna M. Brandner, Jorg Piontek, Dorothee Gunzel
Summary: The formation of tight junction (TJ) is crucial for epidermal barrier function. Manipulation of TJ barriers in reconstructed human epidermis (RHE) was achieved through knockdown of claudin-1 and -4 or by using claudin-binding fusion proteins. The study demonstrates the critical role of claudin-1 in regulating paracellular permeability in the viable epidermis.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Physiology
Natalia Kriuchkova, Tilman Breiderhoff, Dominik Mueller, Duygu Elif Yilmaz, Hasan Demirci, Hoora Drewell, Dorothee Guenzel, Nina Himmerkus, Markus Bleich, Pontus B. Persson, Kerim Mutig
Summary: Perturbed calcium homeostasis in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) limits life expectancy. FHHNC is caused by loss-of-function mutations in CLDN16 or CLDN19 genes, leading to impaired paracellular reabsorption of divalent cations in the cortical thick ascending limb (cTAL). Furosemide, a loop diuretic, can compensate for this impairment by activating Ca2+ transport proteins in the distal nephron and collecting duct, resulting in reduced hypercalciuria.
Article
Physiology
Dorothee Guenzel
Summary: The concept of solvent drag involves the frictional coupling between water and solutes in the same pore for transport. It has been applied to transport processes across cell membranes and along the paracellular pathway. Water-driven solute transport has been proposed as the major mechanism for absorption in the small intestine and reabsorption in the renal proximal tubule. However, the discovery of aquaporins and the claudin protein family has led to a reassessment of the solvent drag concept for transepithelial water and solute transport.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Review
Urology & Nephrology
Luca Meoli, Dorothee Guenzel
Summary: Sequential expression of claudins in the nephron mirrors the sequential expression of ion channels and transporters, contributing to the maintenance of electrolyte and water homeostasis. The regulation and dysregulation of claudins have been extensively studied in the gastrointestinal tract, but their role in the kidney is only just emerging. Investigating the role of claudins in kidney diseases may provide insights into potential prognostic markers or druggable targets.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Multidisciplinary Sciences
Matthias Wuttke, Eva Koenig, Maria-Alexandra Katsara, Holger Kirsten, Saeed Khomeijani Farahani, Alexander Teumer, Yong Li, Martin Lang, Burulca Goecmen, Cristian Pattaro, Dorothee Guenzel, Anna Koettgen, Christian Fuchsberger
Summary: A genotype imputation approach was applied to whole exome sequencing data from the UK Biobank, resulting in the discovery of 158 rare variants and 105 genes significantly associated with kidney function traits. This approach boosts statistical power and provides a comprehensive resource for directing experimental and clinical studies of kidney disease.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Ayk Waldow, Laura-Sophie Beier, Janine Arndt, Simon Schallenberg, Claudia Vollbrecht, Philip Bischoff, Marti Farrera-Sal, Florian N. Loch, Christian Bojarski, Michael Schumann, Lars Winkler, Carsten Kamphues, Lukas Ehlen, Joerg Piontek
Summary: Claudins regulate paracellular permeability, contribute to epithelial polarization and are dysregulated during inflammation and carcinogenesis. Variants of the claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) are highly sensitive protein ligands for generic detection of a broad spectrum of claudins. This study used cCPE fusion proteins to specifically and efficiently detect claudin expression, localization and tight junction dysregulation in various models of gastrointestinal epithelia.
Article
Biochemistry & Molecular Biology
Santhosh Kumar Nagarajan, Stanislav Klein, Bita Sokhandan Fadakar, Joerg Piontek
Summary: Claudin proteins are crucial for regulating paracellular permeability in tight junctions. The architectural models of claudin-10b and claudin-15 suggest an octameric-interlocked-barrels structure, which contributes to their functional differences in ion and water permeability.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Tatjana Zejc, Jorg Piontek, Jorg-Dieter Schulzke, Michael Fromm, Jurgen Ervens, Rita Rosenthal
Summary: The study compares the expression of claudins in oral squamous cell carcinoma (OSCC) and healthy oral epithelium, and finds that the expression levels of claudin-2, -4, and -7 are associated with the diagnosis and prognosis of OSCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sebastian Sewerin, Jorg Piontek, Ria Schonauer, Sonja Grunewald, Angelika Rauch, Steffen Neuber, Carsten Bergmann, Dorothee Gunzel, Jan Halbritter
Summary: This study investigated the molecular basis and phenotypic consequences of a CLDN10 gene variant, which disrupts the assembly of tight junction (TJ) strands. The mutant proteins compromised the function of TJ and exhibited tissue-specific insertion into TJs.
