Review
Biochemistry & Molecular Biology
Eleanor Martin, Rossana Girardello, Gunnar Dittmar, Alexander Ludwig
Summary: Cell polarity is a fundamental property of most animal cells and is crucial for development and tissue functions. Key processes in establishing a polarized epithelial phenotype include rearrangements of the cell cytoskeleton, membrane trafficking, and cell signaling pathways, with Par, Crumbs, and Scribble modules at the core of this regulatory network.
Article
Biochemistry & Molecular Biology
Julia Fiedler, Thomas Moennig, Johanna H. Hinrichs, Annika Weber, Thomas Wagner, Tim Hemmer, Rita Schroeter, Thomas Weide, Daniel Epting, Carsten Bergmann, Pavel Nedvetsky, Michael P. Krahn
Summary: The conserved protein PATJ stabilizes the Crumbs-Pals1 complex to regulate polarity and tight junction formation. In this study, it was found that PATJ interacts with and inhibits HDAC7. Inhibition of HDAC7 restores polarity and lumen formation in epithelial cells. The main function of the Pals1-PATJ complex is to modulate the transcriptional profile of epithelial cells by inhibiting HDAC7.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Cell Biology
Clare E. Buckley, Daniel St Johnston
Summary: Apical-basal polarity is crucial for the form and function of epithelial cells, determining cell adhesion, barrier function, specific cargo secretion, and cytoskeletal organization. Conserved polarity factors play important roles in establishing and maintaining apical-basal polarity, although different mechanisms may be involved in different epithelial tissues.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Article
Biology
Maria Danielle Sallee, Melissa A. Pickett, Jessica L. Feldman
Summary: Research on developing Caenorhabditis elegans intestines reveals the importance of the apical PAR complex in maintaining intestinal epithelial integrity and constructing a functional tube. Depletion of PAR-6, PKC-3, and CDC-42 regulators leads to gaps in apical proteins, hindering food passage and causing larval death.
Article
Biology
Lili Zhang, Xiangyun Wei
Summary: Neurulation is the process of transforming the neuroectoderm into the neural tube. This transformation relies on reorganising the relationships between neighboring cells' intrinsic polarities. Orientational cell adhesions (OCAs) play a crucial role in establishing, maintaining, and modulating these relationships. By comparing neurulation among different species, it is revealed that antiparallel OCAs are a conserved mechanism for neural tube fusion.
BIOLOGICAL REVIEWS
(2023)
Article
Medicine, General & Internal
Deborah Delbue, Lydia Lebenheim, Danielle Cardoso-Silva, Violaine Dony, Susanne M. Krug, Jan F. Richter, Subhakankha Manna, Melba Munoz, Kerstin Wolk, Claudia Heldt, Markus M. Heimesaat, Robert Sabat, Britta Siegmund, Michael Schumann
Summary: IL-22 impairs intestinal epithelial cell barrier by inducing EMT, causing defects in epithelial cell polarity and increasing cell motility and cell invasion. IL-22 modulates TJ protein expression and mediates tight junctional (TJal) barrier defects via ERK pathway.
FRONTIERS IN MEDICINE
(2021)
Article
Developmental Biology
Mingxi Yu, Xinlong Jiang, Wenyang Cai, Xiao Yang, Wenzhong An, Mei Zhang, Yan Xu, Bochuan Zhang, Shuang Tang
Summary: In mouse preimplantation embryos, PATJ and MPDZ are key members of the CRB-PALS1-PATJ apical polarity complex, essential for cell polarization and stabilization of apical junctions. Depletion of PATJ and MPDZ leads to impaired blastocyst formation, compromised trophectoderm differentiation and breakdown of apical domain, tight junctions, and actin filaments.
Article
Biochemistry & Molecular Biology
Shotaro Sakakibara, Ayuko Sakane, Takuya Sasaki, Masakazu Shinohara, Tomohiko Maruo, Muneaki Miyata, Kiyohito Mizutani, Yoshimi Takai
Summary: This study reveals the role of lysophosphatidic acid (LPA) in promoting the organization of the apical junctional complex (AJC). LPA acts through the LPA receptor 1/5 and activates the diacylglycerol-novel PKC and Rho-ROCK pathways to mediate AJC organization, independently of myosin II-induced actomyosin contraction.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Cell Biology
Klaus Ebnet, Volker Gerke
Summary: Membrane polarity, regulated by polarized membrane trafficking and the presence of intramembrane diffusion barriers, is crucial for the development of multicellular tissues. Rho and Rab family small GTPases play important roles in cell-cell junction formation and polarized membrane traffic.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kazuto Tsukita, Manabu Kitamata, Hiroka Kashihara, Tomoki Yano, Ikuko Fujiwara, Timothy F. Day, Tatsuya Katsuno, Jaewon Kim, Fumiko Takenaga, Hiroo Tanaka, Sungsu Park, Makoto Miyata, Hitomi Watanabe, Gen Kondoh, Ryosuke Takahashi, Atsushi Tamura, Sachiko Tsukita
Summary: Liquid-liquid phase separation (LLPS) plays a role in dynamic biological phenomena. In this study, the role of LLPS in the dynamic regulation of junctional actin filaments in epithelial cells was investigated. The researchers identified a multifunctional actin nucleator called cordon bleu (Cobl) as an AJC-enriched microtubule-associated protein and conducted comprehensive in vitro and in vivo analyses. They found that apical microtubules promoted LLPS of Cobl at the AJC, leading to increased Cobl actin assembly activity and spatiotemporal regulation of junctional actin assembly for epithelial morphogenesis and paracellular barriers.
Article
Gastroenterology & Hepatology
Amy C. Engevik, Evan S. Krystofiak, Izumi Kaji, Anne R. Meyer, Victoria G. Weis, Anna Goldstein, Alexander W. Coutts, Tamene Melkamu, Milena Saqui-Salces, James R. Goldenring
Summary: The study investigates the role of Myosin Vb (MYO5B) in cell polarity and the formation of inclusions in microvillus inclusion disease (MVID). The results show that the altered localization of apical polarity proteins and tight junction proteins occurs after loss of Myo5b, both in mouse models and a swine model of MVID. This suggests a potential mechanism for tight junction protein accumulation in MVID patients.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Airah Javorsky, Patrick O. Humbert, Marc Kvansakul
Summary: Cell polarity refers to the asymmetric distribution of biomacromolecules that enable correct orientation of a cell. Viral infections can lead to dysregulation of polarity by interfering with cell polarity regulatory proteins. Understanding viral effector proteins' mechanisms of action on cell polarity can lead to therapeutic interventions and enhance our understanding of tissue homeostasis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Susana Lechuga, Alexander X. Cartagena-Rivera, Afshin Khan, Bert Crawford, Vani Narayanan, Daniel E. Conway, Jaakko Lehtimaki, Pekka Lappalainen, Florian Rieder, Michelle S. Longworth, Andrei I. Ivanov
Summary: The actomyosin cytoskeleton plays a crucial role in maintaining and remodeling epithelial barriers. UNC-45A, a cytoskeletal chaperone, is found to be important in the assembly of myosin structures and the protection of the intestinal epithelial barrier. Decreased expression of UNC-45A in patients with ulcerative colitis may contribute to barrier disruption and worsen the symptoms of the disease.
Article
Cell Biology
Galym Ismagulov, Sofiane Hamidi, Guojun Sheng
Summary: During mammalian embryo development, cellular morphogenesis resembling EMT and MET transitions play a crucial role in shaping the three-dimensional structure. The integration of pluripotency regulation, morphogenetic signaling, and biomechanical force anisotropy drives the organization of the embryonic 3-D structure. Investigating the molecular regulation of epithelial cell polarity and partial EMT/MET is important for understanding mammalian early development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Batiste Boeda, Vincent Michel, Raphael Etournay, Patrick England, Stephane Rigaud, Heloise Mary, Samy Gobaa, Sandrine Etienne-Manneville
Summary: Using an organ-on-chip model, this study elucidates the role of SCRIB in controlling cell and tissue shape during gut epithelium differentiation. The results show that SCRIB acts as a scaffold for SHROOM2/4 and ROCK1, controlling myosin polarization and playing a critical role in apical cell shape and epithelial morphogenesis.
JOURNAL OF CELL BIOLOGY
(2023)
Letter
Ophthalmology
Ivan Seah, Xin Xin Zhao, Qianyu Lin, Zengping Liu, Steven Zheng Zhe Su, Yew Sen Yuen, Walter Hunziker, Gopal Lingam, Xian Jun Loh, Xinyi Su
Review
Biochemistry & Molecular Biology
Eleanor Martin, Rossana Girardello, Gunnar Dittmar, Alexander Ludwig
Summary: Cell polarity is a fundamental property of most animal cells and is crucial for development and tissue functions. Key processes in establishing a polarized epithelial phenotype include rearrangements of the cell cytoskeleton, membrane trafficking, and cell signaling pathways, with Par, Crumbs, and Scribble modules at the core of this regulatory network.
Article
Gastroenterology & Hepatology
Jianliang Xu, P. Jaya Kausalya, Noemi Van Hul, Matias J. Caldez, Shiyi Xu, Alicia Ghia Min Ong, Wan Lu Woo, Safiah Mohamed Ali, Philipp Kaldis, Walter Hunziker
Summary: The study highlights the crucial role of Tjp2 in maintaining liver tissue barriers and bile transport processes. Deficiency in Tjp2 can lead to the formation of a model for cholestatic liver disease, and certain drugs such as ursodeoxycholic acid and 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene can partially alleviate this damage.
Article
Cell & Tissue Engineering
Zengping Liu, Bhav Harshad Parikh, Queenie Shu Woon Tan, Daniel Soo Lin Wong, Kok Haur Ong, Weimiao Yu, Ivan Seah, Graham E. Holder, Walter Hunziker, Gavin S. W. Tan, Veluchamy Amutha Barathi, Gopal Lingam, Boris Stanzel, Timothy A. Blenkinsop, Xinyi Su
Summary: Studies have shown that human RPE stem cell-derived RPE transplantation can restore vision, survive for a long period in experimental animal models, and is safe and reliable, providing a potential effective source for RPE cell replacement therapy.
Article
Nanoscience & Nanotechnology
Fang Yu, Nivasini Selva Kumar, Satnam Singh, Walter Hunziker, Sum Huan Ng, Deepak Choudhury
Summary: A microfluidic immunopanning chip (MIC) has been developed for simultaneous isolation and purification of multiple types of primary brain microvascular cells, achieving higher efficiency and purity compared to conventional methods. Incorporation of microcarriers in the MIC increases cell capturing efficiency and serves as a substrate for subsequent cell culture. With low reagents consumption, multiplexing capabilities, and high isolation efficiency, the MIC shows great potential for rare cell isolation and broader applications in cell therapy.
MICROFLUIDICS AND NANOFLUIDICS
(2021)
Article
Cell & Tissue Engineering
Swathi Lingam, Zengping Liu, Binxia Yang, Wendy Wong, Bhav Harshad Parikh, Jun Yi Ong, Debbie Goh, Daniel Soo Lin Wong, Queenie Shu Woon Tan, Gavin S. W. Tan, Graham E. Holder, Kakkad Regha, Veluchamy Amutha Barathi, Walter Hunziker, Gopal Lingam, Xianmin Zeng, Xinyi Su
Summary: The study evaluated the therapeutic potential of induced pluripotent stem cell (iPSC)-derived photoreceptor precursors in non-human primates. The results demonstrated good biocompatibility in naive models and the ability of the cells to survive and mature into cone photoreceptors in the damaged models. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation, indicating the safety and therapeutic potential of these clinically compliant iPSC-derived cells.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Pharmacology & Pharmacy
Tze Ker Matthew Leong, Wen Shern Lo, Wei En Zen Lee, Benedict Tan, Xing Zhao Lee, Li Wen Justina Nadia Lee, Jia-Ying Joey Lee, Nivedita Suresh, Lit-Hsin Loo, Evan Szu, Joe Yeong
Summary: Cancer is the leading cause of death globally, with efforts to understand the complex and heterogeneous tumor microenvironment (TME) being crucial for research into this disease. Utilizing in vitro tumor models and artificial intelligence to study the TME holds great potential, but faces limitations such as inadequate data and ethical concerns. Overcoming these limitations is essential for future research to improve clinical outcomes.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Xinxin Zhao, Ivan Seah, Kun Xue, Wendy Wong, Queenie Shu Woon Tan, Xiaoxiao Ma, Qianyu Lin, Jason Y. C. Lim, Zengping Liu, Bhav Harshad Parikh, Karishma N. Mehta, Joel Weijia Lai, Binxia Yang, Kim Chi Tran, Veluchamy Amutha Barathi, Kang Hao Cheong, Walter Hunziker, Xinyi Su, Xian Jun Loh
Summary: This study introduces a novel nanomicelle drug delivery system that can deliver anti-VEGF drugs to the posterior segment of the retina through corneal-scleral routes, showing significant therapeutic effects. Additionally, the delivery system demonstrates biocompatibility and intrinsic antiangiogenic properties, suggesting promising potential for the treatment of retinal diseases.
ADVANCED MATERIALS
(2022)
Article
Cell Biology
Deborah Neyrinck-Leglantier, Julien Lesage, Silvia Blacher, Arnaud Bonnomet, Walter Hunziker, Agnes Noel, Valerian Dormoy, Beatrice Nawrocki-Raby, Christine Gilles, Myriam Polette
Summary: The delocalization of ZO-1 from tight junctions plays a significant role in epithelial cell plasticity during tumor progression, impacting the secretion of pro-inflammatory chemokines and promoting immune cell recruitment in vivo. High densities of CD8 cytotoxic T cells and Foxp3 immunosuppressive regulatory T cells in the tumor microenvironment were correlated with cyto-nuclear expression of ZO-1, suggesting a potential role in tumor progression by recruiting immune cells through affecting tumor cell secretome.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Barbara Hubner, Eric von Otter, Bilal Ahsan, Mei Ling Wee, Sara Henriksson, Alexander Ludwig, Sara Sandin
Summary: This study provides ultrastructural insight into the architecture of telomeres using correlative light and electron microscopy. The researchers discovered marked differences in telomere size, shape, and chromatin compaction between cancer and non-cancer cells. They also found that telomeres are in direct contact with other heterochromatin regions.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Microbiology
Ronni A. G. da Silva, Wei Hong Tay, Foo Kiong Ho, Frederick Reinhart Tanoto, Kelvin K. L. Chong, Pei Yi Choo, Alexander Ludwig, Kimberly Kline
Summary: This study describes the intracellular survival mechanisms of Enterococcus faecalis, a pathogen frequently found in chronic wounds. The researchers found that E. faecalis can survive and replicate inside immune cells and non-immune cells during wound infection, potentially contributing to chronic infections. The bacteria are taken up by host cells primarily through macropinocytosis and manipulate the endosomal pathway to avoid lysosomal degradation and death. The findings provide insights into E. faecalis pathogenesis and highlight the diversity of mechanisms bacteria use to evade host-mediated killing.
Article
Cell Biology
Stine Kjaer Morthorst, Camilla Nielsen, Pietro Farinelli, Zeinab Anvarian, Christina Birgitte R. Rasmussen, Andrea Serra-Marques, Ilya Grigoriev, Maarten Altelaar, Nicoline Furstenberg, Alexander Ludwig, Anna Akhmanova, Soren Tvorup Christensen, Lotte Bang Pedersen
Summary: A new interactor of KIF13B, Ap80, has been identified, which promotes the binding of PALS1 to KIF13B and regulates ciliary length, composition and signaling.
JOURNAL OF CELL SCIENCE
(2022)
Article
Physics, Multidisciplinary
Thuan Beng Saw, Xumei Gao, Muchun Li, Jianan He, Anh Phuong Le, Supatra Marsh, Keng-hui Lin, Alexander Ludwig, Jacques Prost, Chwee Teck Lim
Summary: This study investigates how the homeostasis of epithelial tissues is modified when a transepithelial potential difference different from the natural one is imposed on them. The researchers find that when the field direction matches the natural one, the perfect confluence of the epithelial layer can be restored and active-cell response is induced. However, when the field is opposite, the homeostasis of the tissue is disrupted.
Article
Biochemical Research Methods
Benedict Tan, Suat Peng, Siti Maryam J. M. Yatim, Jayantha Gunaratne, Walter Hunziker, Alexander Ludwig