Review
Physiology
Il Hwan Oh, Chor Ho Jo, Sua Kim, Sungsin Jo, Sungjin Chung, Gheun-Ho Kim
Summary: The study revealed that metabolic acidosis-induced hypercalciuria and hypermagnesiuria are due to the down-regulation of claudin-16 and claudin-19 in the thick ascending limb via the calcium-sensing receptor and can be reversed by the calcium-sensing receptor antagonist. These findings contribute to understanding the regulatory role of paracellular tight junction proteins in the thick ascending limb.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Henrik Dimke, Camille Griveau, Wung-Man Evelyne Ling, Gaelle Brideau, Lydie Cheval, Pravina Muthan, Dominik Mueller, Amr Al-Shebel, Pascal Houillier, Caroline Prot-Bertoye
Summary: The kidney plays a critical role in maintaining mineral balance in the body. Dysregulation of calcium and magnesium reabsorption in the renal tubules can lead to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), which is characterized by excessive wasting of calcium and magnesium. This study investigated the localization of claudin-19 (CLDN19), a protein involved in mineral reabsorption, in the kidneys and found that it is primarily located in the basolateral membrane of the renal tubules. Additionally, the study showed that CLDN19 interacts with claudin-16 (CLDN16) to regulate permeability in the tubules. These findings provide insights into the pathophysiology of FHHNC and highlight the importance of CLDN19 in maintaining mineral homeostasis in the kidney.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Multidisciplinary Sciences
Catarina Quintanova, Nina Himmerkus, Samuel L. Svendsen, Otto von Schwerdtner, Cosima Merkel, Lennart Pinckert, Kerim Mutig, Tilman Breiderhoff, Dominik Mueller, Dorothee Guenzel, Markus Bleich
Summary: Claudin-10b is an important component of the tight junction and allows paracellular sodium transport in the thick ascending limb of Henle's loop. It colocalizes with the basolateral Na+-K+ ATPase and the Cl- channel subunit barttin, and its absence increases the accessibility of the basolateral extracellular space to certain substances. Electron microscopy reveals a widening of basolateral membrane infoldings in the absence of Claudin-10b. These findings suggest that Claudin-10b may shape neighboring membrane invaginations through trans interaction, thereby stabilizing and facilitating high-flux salt transport.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
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
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
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)
Review
Multidisciplinary Sciences
Pascal Houillier, Loic Lievre, Marguerite Hureaux, Caroline Prot-Bertoye
Summary: Magnesium is crucial for many biological processes, including energy release. Paracellular transport is essential for magnesium homeostasis, and pathogenic variants in CLDN genes have been found to disturb this process. CLDN16 or CLDN19 loss of function leads to familial hypomagnesemia, while pathogenic CLDN10 variants cause HELIX syndrome, characterized by renal loss of sodium chloride and hypermagnesemia. This review summarizes the current knowledge of paracellular magnesium permeability and outlines some unresolved questions.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Physiology
Andree-Anne Marcoux, Laurence E. Tremblay, Samira Slimani, Marie-Jeanne Fiola, Fabrice Mac-Way, Ludwig Haydock, Alexandre P. Garneau, Paul Isenring
Summary: The loop of Henle plays important physiological roles in regulating extracellular fluid volume, blood pressure, ion balance, urinary concentration, and tubuloglomerular feedback. Recent studies have also highlighted its role in the renal-sparing effect of SGLT2 inhibitors.
COMPREHENSIVE PHYSIOLOGY
(2022)
Article
Ophthalmology
Aihua Hou, Safiah Mohamed Ali, Evelyn Png, Walter Hunziker, Louis Tong
Summary: The purpose of this study was to investigate the role of TG-2 in corneal barrier function and its regulation of epithelial junctional proteins and transcription factors. Corneas from TG-2-/- mice showed lower trans-epithelial electrical resistance and increased central corneal thickness compared to TG-2+/+ mice. TG-2-/- mice also exhibited a faster increase in fluorescence in the anterior chamber after ocular exposure to FITC-dextran. The expression of Claudin-1 protein and transcript levels were reduced in the cornea of TG-2-/- mice and in TG-2 knockdown human corneal epithelial cells.
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)
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
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
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
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
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)