Article
Biology
Airah Javorsky, Patrick O. Humbert, Marc Kvansakul
Summary: The study reveals that SARS-CoV-1 and SARS-CoV-2 E proteins can interfere with cell polarity and cell-cell junction integrity in human epithelial cells by binding to the PALS1 PDZ domain, potentially leading to disease symptoms. These findings provide insights for the development of small molecule inhibitors against SARS-CoV-1/2 in the future.
COMMUNICATIONS BIOLOGY
(2021)
Review
Cell Biology
Joseph Jose Thottacherry, Jia Chen, Daniel St Johnston
Summary: Apical-basal polarity is crucial for the form and function of intestinal epithelial cells, which form a single layer in the gut and have distinct apical, lateral, and basal domains. The occluding junctions at the apical side of the lateral domains play a crucial role in maintaining tissue homeostasis, protecting against gastrointestinal pathogens, and supporting immune response. While most epithelial cells establish apical-basal polarity through conserved polarity factors, recent studies suggest novel mechanisms in gut epithelium polarization. This review discusses the advances in understanding polarity factors, focusing on studies in C. elegans, Drosophila, Zebrafish, and Mouse.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
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
Cell Biology
Antonio E. Paniagua, Alicia Segurado, Jorge F. Dolon, Julian Esteve-Rudd, Almudena Velasco, David S. Williams, Concepcion Lillo
Summary: The study reveals that CRB2 plays a crucial role in the polarization process of human RPE cells, contributing to tight junction maintenance and cell cycle arrest. Knockdown of CRB2 in RPE cells affects the distribution of apical polarity proteins and disrupts retinal homeostasis by causing invasion of activated microglial cells into the subretinal space. Overall, CRB2 is identified as a key protein for the development and maintenance of a polarized epithelium.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Joanna Szczurkowska, Alan Guo, Jacqueline Martin, Seong-Il Lee, Edward Martinez, Chia Te Chien, Tamor A. Khan, Ravnit Singh, Doreen Dadson, Tracy S. Tran, Sophie Pautot, Maya Shelly
Summary: This study identifies the extrinsic cues and intrinsic determinants involved in the polarization of neuronal apical dendrites, and reveals the underlying molecular mechanism.
Article
Biochemistry & Molecular Biology
Naomi J. Stolpner, Nadia I. Manzi, Thomas Su, Daniel J. Dickinson
Summary: During embryonic development, cell division orientation is important for tissue growth and cell fate specification. Polarity proteins play a role in controlling cell division orientation by interacting with microtubule regulators. In C. elegans, polarity proteins dynamically localize and contribute to spindle orientation and cell positioning. Interestingly, isolated single blastomeres can also form polarity caps, which can regulate spindle orientation even without cell contacts.
Article
Developmental Biology
Tamor A. Khan, Alan Guo, Jacqueline Martin, Chia Te Chien, Tianrui Liu, Joanna Szczurkowska, Maya Shelly
Summary: Previous studies suggested that axon formation precedes and is necessary for neuronal polarization, but recent evidence suggests that bipolar polarity and apical dendrite development can occur when axon formation is prevented.
DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Piyumi Wijesekara, Prakarsh Yadav, Lydia A. Perkins, Donna B. Stolz, Jonathan M. Franks, Simon C. Watkins, Emily Reinoso Jacome, Steven L. Brody, Amjad Horani, Jian Xu, Amir Barati Fariman, Xi Ren
Summary: This study described a reproducible engineering method to obtain apical-out airway organoids from cells. Using computer vision algorithms, a computational framework was developed to quantify the rotation of these organoids and correlate it with cilia motility. The feasibility of using this rotating model to recapitulate and measure defective cilia motility was further demonstrated.
Article
Biochemistry & Molecular Biology
Jean-Baptiste Brault, Sabine Bardin, Marusa Lampic, Jacopo A. Carpentieri, Laure Coquand, Maxime Penisson, Hugo Lachuer, Guiliana Soraya Victoria, Sarah Baloul, Fatima El Marjou, Gaelle Boncompain, Stephanie Miserey-Lenkei, Richard Belvindrah, Vincent Fraisier, Fiona Francis, Franck Perez, Bruno Goud, Alexandre D. Baffet
Summary: This study reveals that the delamination process of radial glial (RG) cells in the developing neocortex is regulated by the post-Golgi secretory pathway. The transport of RAB6+ vesicles towards the minus ends of microtubules depends on dynein, and the apical determinant Crumbs3 (CRB3) is also transported by dynein. Knockout of RAB6A/A' and RAB6B, as well as LIS1, impairs the apical localization of CRB3 and leads to delamination and ectopic division of aRG cells.
Editorial Material
Biochemistry & Molecular Biology
Tony J. C. Harris
Summary: A new study reveals that the initial symmetry break in Drosophila anterior-posterior axis specification is induced by a posterior domain of cortical myosin with unique post-translational modification and dynamics, which in turn recruits downstream posterior determinants.
Article
Multidisciplinary Sciences
Nataliia Konstantinova, Lukas Hoermayer, Matous Glanc, Rabab Keshkeih, Shutang Tan, Martin Di Donato, Katarzyna Retzer, Jeanette Moulinier-Anzola, Max Schwihla, Barbara Korbei, Markus Geisler, Jiri Friml, Christian Luschnig
Summary: The authors of this study reveal the involvement of WAV3 E3 ubiquitin ligases in determining the polarity of PIN proteins in Arabidopsis. They show that WAV3 E3 ligases selectively antagonize the ectopic deposition of newly synthesized PIN proteins, maintaining the polar localization of PIN proteins.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Pu Zhang, Taylor N. Medwig-Kinney, Bob Goldstein
Summary: Zhang, Medwig-Kinney, and Goldstein show that the medioapical actomyosin network driving apical constriction in C. elegans gastrulation has a diffuse organization with a mixed-polarity actin filament network. This differs from the sarcomere-like architecture observed in the Drosophila ventral furrow. They further demonstrate that C. elegans endodermal precursor cells apically constrict using a mixed-polarity actin filament network and with myosin and myosin activator distributed throughout the network. These results suggest that diverse actomyosin architectures are used in animal cells to accomplish apical constriction.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Julia Harms, Simona Mareike Luettgenau, Christin Emming, Justine Guske, Katrin Weber, Thomas Wagner, Larissa Schowe, Pavel Nedvetsky, Michael P. P. Krahn
Summary: The downregulation of tight junction adapter protein Pals1 in colorectal cancer cells leads to increased cell migration, invasion, and metastasis. The researchers found a redundancy between Arf6-GAP SMAP1 and Pals1 in regulating the activation of Arf6/Rac1 and controlling cell migration. Furthermore, the downregulation of both SMAP1 and Pals1 results in enhanced cell migration and invasion.
CANCER GENE THERAPY
(2022)
Article
Cell Biology
Sergio Simoes, Gerald Lerchbaumer, Milena Pellikka, Paraskevi Giannatou, Thomas Lam, Dohyun Kim, Jessica Yu, David ter Stal, Kenana Al Kakouni, Rodrigo Fernandez-Gonzalez, Ulrich Tepass
Summary: Most forms of cancer involve the movement of cells out of an epithelial layer, a process that requires the loss of apical polarity. This study reveals the regulatory role of key polarity proteins in this loss of polarity. The dynamic regulation of the apical Crumbs polarity complex is crucial for normal neural stem cell ingression.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biology
Jia Chen, Daniel St Johnston
Summary: In the adult Drosophila midgut, the process of enteroblast integration resembles lumen formation in mammalian epithelial cysts, with enteroblasts forming a pre-assembled apical compartment and an apical membrane initiation site (AMIS) before integrating into the epithelium.
Article
Medicine, Research & Experimental
Thilo M. Buck, Rogier M. Vos, C. Henrique Alves, Jan Wijnholds
Summary: Loss of Crumbs homolog 1 (CRB1) or CRB2 proteins in Muller cells or photoreceptors in the mouse retina results in a CRB dose-dependent retinal phenotype. A novel Muller cell-specific Crb1(KO)Crb2(LowMGC) retinitis pigmentosa mouse model showed deficits in electroretinography and retinal morphology. Expressing human CRB2 (hCRB2) in Muller cells was more effective in preventing vision loss than expressing human CRB1 (hCRB1), indicating the importance of hCRB expression in Muller cells for maintaining retinal structure and function.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Ophthalmology
Mays Talib, Mary J. van Schooneveld, Jan Wijnholds, Maria M. van Genderen, Nicoline E. Schalij-Delfos, Herman E. Talsma, Ralph J. Florijn, Jacoline B. ten Brink, Frans P. M. Cremers, Alberta A. H. J. Thiadens, L. Ingeborgh van den Born, Carel B. Hoyng, Magda A. Meester-Smoor, Arthur A. Bergen, Camiel J. F. Boon
Summary: This study investigated the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and explored potential clinical endpoints. Despite a generally severe course, symptom onset and central visual function varied, even at advanced ages. Phenotypes may differ within the same family, and longitudinal imaging and functional studies are needed to determine appropriate endpoints for a clinical trial.
ACTA OPHTHALMOLOGICA
(2021)
Article
Urology & Nephrology
Annika Moller-Kerutt, Juan E. Rodriguez-Gatica, Karin Wacker, Rohan Bhatia, Jan-Peter Siebrasse, Nanda Boon, Veerle Van Marck, Peter Boor, Ulrich Kubitscheck, Jan Wijnholds, Hermann Pavenstadt, Thomas Weide
Summary: Mutations in the CRB2 gene can cause SRNS, and CRB2 is an essential component of podocyte slit diaphragm, interacting with Nephrin. Crb2(podKO) mice exhibit proteinuria, disordered foot processes, and increased renal injury and inflammatory markers.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nanda Boon, C. Henrique Alves, Aat A. Mulder, Charlotte A. Andriessen, Thilo M. Buck, Peter M. J. Quinn, Rogier M. Vos, Abraham J. Koster, Carolina R. Jost, Jan Wijnholds
Summary: Mutations in the Crb1 gene lead to retinal diseases in rats, causing characteristic retinal changes and decreased visual acuity. Subretinal injection of AAV5 and AAV9 predominantly infect RPE and photoreceptor cells in mutant rats, while intravitreal injection of ShH10(Y445F) mainly infects Muller glial cells. Gene therapy using AAV vectors did not improve retinal function in Crb1 mutant rats, indicating the need for earlier expression of recombinant hCRB proteins in Muller glial cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Wida Razawy, Celso H. Alves, Marijke Koedam, Patrick S. Asmawidjaja, Adriana M. C. Mus, Mohamed Oukka, Pieter J. M. Leenen, Jenny A. Visser, Bram C. J. van der Eerden, Erik Lubberts
Summary: The deficiency of IL-23R results in temporal and long-term changes in bone growth, including lower bone mass and more fragile bones in mice. However, it does not significantly affect osteoclast differentiation and resorption capacity, but mainly influences the bone formation process.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Lynn Nazareth, James St John, Mariyam Murtaza, Jenny Ekberg
Summary: The central nervous system has limited regenerative capacity, while the peripheral nervous system has greater ability for regeneration due to differences in glial-mediated functions. Schwann cells and olfactory ensheathing cells play important roles in phagocytosis and clearance of debris in nerve regeneration and injury.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemical Research Methods
Stephen A. Wood, Peter G. Hains, Arnaud Muller, Melissa Hill, Susitha Premarathne, Mariyam Murtaza, Phillip J. Robinson, George D. Mellick, Alex M. Sykes
Summary: In this study, we quantified proteomic differences between healthy control and PD patient cells and identified the critical role of the unfolded protein response (UPR) in PD patients. PD patients with high amounts of PDIA6 and HYOU1 proteins were more sensitive to endoplasmic reticulum stress. These findings provide insight into underlying cellular dysfunctions in PD patients.
PROTEOMICS CLINICAL APPLICATIONS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Peter M. J. Quinn, Antonio Francisco Ambrosio, Celso Henrique Alves
Article
Biochemistry & Molecular Biology
Ines Ramos Rego, Daniela Silverio, Maria Isabel Eufrasio, Sandra Sofia Pinhancos, Bruna Lopes da Costa, Jose Teixeira, Hugo Fernandes, Yang Kong, Yao Li, Stephen H. Tsang, Paulo J. Oliveira, Rosa Fernandes, Peter M. J. Quinn, Paulo Fernando Santos, Antonio Francisco Ambrosio, Celso Henrique Alves
Summary: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness in the elderly. The damage to retinal pigment epithelium (RPE) caused by oxidative stress is a key factor in the development of AMD, and this damage is caused by the accumulation of reactive oxygen species (ROS) primarily produced by mitochondria. The protein TRAP1, found in mitochondria, helps maintain mitochondrial integrity and reduces ROS production. This study found that TRAP1 is present in human RPE cells and its levels decrease when exposed to hydrogen peroxide. Silencing TRAP1 leads to increased ROS production and decreased mitochondrial respiratory capacity in RPE cells.
Review
Biochemistry & Molecular Biology
Ronak Reshamwala, Mariyam Murtaza, Mo Chen, Megha Shah, Jenny Ekberg, Dinesh Palipana, Marie-Laure Vial, Brent McMonagle, James St John
Summary: This position paper provides an in-depth analysis of previous clinical trials using olfactory ensheathing cell (OEC) transplantation for spinal cord injury (SCI) repair, and proposes strategies to improve standardization of OEC therapies. The paper aims to serve as a roadmap for designing effective clinical trials with OEC transplantation-based therapy for SCI repair.
Article
Genetics & Heredity
Joao Pedro Marques, Ricardo Machado Soares, Silvia Simao, Rebhi Abuzaitoun, Chris Andrews, C. Henrique Alves, Antonio Francisco Ambrosio, Joaquim Murta, Rufino Silva, Maria Fernanda Abalem, K. Thiran Jayasundera
Summary: The purpose of this study was to evaluate the self-reported visual function and psychosocial impact of visual loss in patients with EYS-associated retinal degeneration. Two patient-reported outcome measures, the MRDQ and MVAQ, were used. The results showed a correlation between the PRO measures and the clinician-reported outcomes.
OPHTHALMIC GENETICS
(2023)
Article
Ophthalmology
Ricardo Machado Soares, Ana Luisa Carvalho, Silvia Simao, Celia Azevedo Soares, Miguel Raimundo, C. Henrique Alves, Antonio Francisco Ambrosio, Joaquim Murta, Jorge Saraiva, Rufino Silva, Joao Pedro Marques
Summary: This study aims to provide detailed information about the natural history, genetic landscape, and phenotypic spectrum of EYS-associated retinal degeneration (EYS-RD). The study identified 8 novel EYS variants and found a high frequency of atypical phenotypes. Patients with atypical RP had better best-corrected visual acuity (BCVA) and larger ellipsoid zone widths, indicating a better prognosis.
OPHTHALMOLOGY RETINA
(2023)
Review
Cell & Tissue Engineering
Mariyam Murtaza, Lipsa Mohanty, Jenny A. K. Ekberg, James A. St John
Summary: Olfactory ensheathing cell transplantation is a promising treatment option for nervous system injuries, but the poor survival of transplanted cells limits its therapeutic efficacy. Therefore, strategies to optimize the survival and integration of OECs are needed.
CELL TRANSPLANTATION
(2022)
Meeting Abstract
Ophthalmology
Mays Talib, Xuan-Thanh-An Nguyen, Mary J. Van Schoon-Eveld, Joost Brinks, Jacoline Ten Brink, Ralph J. Florijn, Jan Wijnholds, Robert M. Verdijk, Arthur A. Bergen, Camiel J. F. Boon
ACTA OPHTHALMOLOGICA
(2021)