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
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)
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
Biochemistry & Molecular Biology
Alessandro Berselli, Giulio Alberini, Fabio Benfenati, Luca Maragliano
Summary: Tight junctions (TJs) are multi-protein complexes that seal the paracellular space between adjacent endothelial or epithelial cells. The Claudin-5 (Cldn5) protein plays a crucial role in the blood-brain barrier (BBB) and little is known about its TJ assemblies. In this study, molecular dynamics simulations were used to investigate the permeation of ions and water through different Cldn5 structures, including a pathogenic mutation. The findings provide insights into the selectivity of BBB's paracellular transport and validate the structural models.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
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.
Review
Biochemistry & Molecular Biology
Alessandro Berselli, Fabio Benfenati, Luca Maragliano, Giulio Alberini
Summary: Claudins (Cldns) are transmembrane proteins that play a major role in tight junction integrity and tissue selectivity. Computational methodologies have been used to investigate the properties of Cldn and provide valuable insights for improving the characterization of Cldn and designing strategies for controlling paracellular transport.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Alessandro Berselli, Fabio Benfenati, Luca Maragliano, Giulio Alberini
Summary: Claudins are transmembrane proteins that play a crucial role in tight junction integrity and tissue selectivity. They form barriers or ion-selective channels between cells in the paracellular space. Computational methodologies have helped to elucidate the properties of Claudins and could be useful for designing strategies to control the transport of drugs or molecules.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Shadi Fuladi, Sarah McGuinness, Fatemeh Khalili-Araghi
Summary: In this study, the behavior of claudin-15 strands within lipid membranes and the effect of a single-point mutation on the morphology of the strands were investigated using molecular dynamics. The results showed that the mutation significantly altered the lateral flexibility of the strands, resulting in a three-fold increase in persistence length. The mutation introduced a bend in the third transmembrane helix, which restricted the fluctuations of the strands and led to higher persistence lengths.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ashley Monaco, Ben Ovryn, Josephine Axis, Kurt Amsler
Summary: The paracellular permeability in epithelial cells involves both a Pore Pathway for small ions and solutes, and a Leak Pathway for larger solutes. While the Pore Pathway is better understood, the proteins and mechanism behind the Leak Pathway remain unresolved and controversial. Further research is needed to clarify the molecular basis and regulation of the Leak Pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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
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
Pharmacology & Pharmacy
Joel Brunner, Sakthikumar Ragupathy, Gerrit Borchard
Summary: Research focuses on modulating intercellular tight junctions to enhance drug absorption and bioavailability, with challenges in commercialization. Target-specific permeation enhancers have potential clinical applications.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Multidisciplinary Sciences
Nandhini Rajagopal, Shikha Nangia
Summary: This study investigates the molecular assembly of claudins, specifically claudin-5 and claudin-15, to determine their structural and functional properties. The research findings suggest that each member of the claudin family has a unique strand architecture that requires systematic molecular-level analysis.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
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
Chemistry, Physical
Isidro Cortes-Ciriano, Guillaume Bouvier, Michael Nilges, Luca Maragliano, Therese E. Malliavin
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2015)
Article
Multidisciplinary Sciences
Letizia Chiodo, Therese E. Malliavin, Luca Maragliano, Grazia Cottone, Giovanni Ciccotti
Article
Multidisciplinary Sciences
Francesco Paonessa, Stefania Criscuolo, Silvio Sacchetti, Davide Amoroso, Helena Scarongella, Federico Pecoraro Bisogni, Emanuele Carminati, Giacomo Pruzzo, Luca Maragliano, Fabrizia Cesca, Fabio Benfenati
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Biochemistry & Molecular Biology
Pia Rossi, Bruno Sterlini, Enrico Castroflorio, Antonella Marte, Franco Onofri, Flavia Valtorta, Luca Maragliano, Anna Corradi, Fabio Benfenati
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Clinical Neurology
Anna Fassio, Alessandro Esposito, Mitsuhiro Kato, Hirotomo Saitsu, Davide Mei, Carla Marini, Valerio Conti, Mitsuko Nakashima, Nobuhiko Okamoto, Akgun Olmez Turker, Burcu Albuz, C. Nur Semerci Gunduz, Keiko Yanagihara, Elisa Belmonte, Luca Maragliano, Keri Ramsey, Chris Balak, Ashley Siniard, Vinodh Narayanan, Chihiro Ohba, Masaaki Shiina, Kazuhiro Ogata, Naomichi Matsumoto, Fabio Benfenati, Renzo Guerrini
Article
Chemistry, Physical
S. Alexis Paz, Luca Maragliano, Cameron F. Abrams
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2018)
Article
Chemistry, Medicinal
Letizia Chiodo, Therese E. Malliavin, Sergio Giuffrida, Luca Maragliano, Grazia Cottone
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2018)
Article
Chemistry, Physical
Giulio Alberini, Fabio Benfenati, Luca Maragliano
JOURNAL OF PHYSICAL CHEMISTRY B
(2018)
Article
Multidisciplinary Sciences
Federica Maiole, Giulia Tedeschi, Simona Candiani, Luca Maragliano, Fabio Benfenati, Letizia Zullo
SCIENTIFIC REPORTS
(2019)
Article
Nanoscience & Nanotechnology
Mattia Lorenzo DiFrancesco, Francesco Lodola, Elisabetta Colombo, Luca Maragliano, Mattia Bramini, Giuseppe Maria Paterno, Pietro Baldelli, Mauro Dalla Serra, Lorenzo Lunelli, Marta Marchioretto, Giorgio Grasselli, Simone Cimo, Letizia Colella, Daniele Fazzi, Fausto Ortica, Vito Vurro, Cyril Giles Eleftheriou, Dmytro Shmal, Jose Fernando Maya-Vetencourt, Chiara Bertarelli, Guglielmo Lanzani, Fabio Benfenati
NATURE NANOTECHNOLOGY
(2020)
Article
Biochemical Research Methods
Stefania Criscuolo, Mahad Gatti Iou, Assunta Merolla, Luca Maragliano, Fabrizia Cesca, Fabio Benfenati
ACS SYNTHETIC BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
L. Chiodo, T. E. Malliavin, L. Maragliano, G. Cottone
BIOPHYSICAL CHEMISTRY
(2017)
Article
Neurosciences
Cyril Eleftheriou, Fabrizia Cesca, Luca Maragliano, Fabio Benfenati, Jose Fernando Maya-Vetencourt
JOURNAL OF EXPERIMENTAL NEUROSCIENCE
(2017)
Review
Neurosciences
Mattia Bramini, Giulio Alberini, Elisabetta Colombo, Martina Chiacchiaretta, Mattia L. DiFrancesco, Jose F. Maya-Vetencourt, Luca Maragliano, Fabio Benfenati, Fabrizia Cesca
FRONTIERS IN SYSTEMS NEUROSCIENCE
(2018)