Article
Multidisciplinary Sciences
Konstantinos Nakos, Md Noor A. Alam, Megan R. Radler, Ilona A. Kesisova, Changsong Yang, Joshua Okletey, Meagan R. Tomasso, Shae B. Padrick, Tatyana M. Svitkina, Elias T. Spiliotis
Summary: Cellular morphogenesis and processes such as cell division and migration require the coordination of the microtubule and actin cytoskeletons. This study shows that septins mediate microtubule-actin crosstalk by coupling actin polymerization to microtubule lattices.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Joao Goncalves
Summary: LUZP1 is a significant protein involved in embryonic development and disease etiology, playing important regulatory roles in cell cycle progression, cell migration, and epithelial cell apical constriction.
EUROPEAN JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell Biology
Manos Mavrakis, M. Angeles Juanes
Summary: Cell movement is influenced by the turnover of focal adhesions, which traditionally was believed to be triggered by microtubules. However, recent research has discovered other molecular players that affect actin cytoskeleton dynamics, enabling directed cell migration.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Review
Cell Biology
Giulia Russo, Michael Krauss
Summary: Cytokinesis involves the final separation of a mother cell into two daughter cells, with septins playing a crucial role in this process. Septins are recruited to the cleavage furrow early on and undergo constant rearrangement during cytokinetic progression, ultimately concentrating within the intercellular bridge. This concentration of septins at specific sites may support cytokinetic progression by interacting with actin, microtubules, and associated motors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fatmanur Tiryaki, Jovana Deretic, Elif Nur Firat-Karalar
Summary: Centrioles and cilia are essential microtubule-based structures in cells that play critical roles in cell function and development. This study identifies a new microtubule-associated protein, ENKD1, which regulates microtubule organization and stability. Furthermore, it shows that ENKD1 depletion leads to defective regulation of ciliary length and content, as well as a failure to respond to Hedgehog pathway activation.
Review
Cell Biology
Ruixin Ge, Minghui Cao, Miao Chen, Min Liu, Songbo Xie
Summary: Primary cilia function as sensory organelles that monitor extracellular signals and transduce them into intracellular responses. Actin and microtubule networks play critical roles in primary ciliogenesis and maintenance. Targeting cytoskeleton-associated proteins may be a promising therapeutic strategy for treating ciliopathies.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biophysics
Shrawan Kumar Mageswaran, Danielle Ann Grotjahn, Xiangrui Zeng, Benjamin Asher Barad, Michaela Medina, My Hanh Hoang, Megan J. Dobro, Yi-Wei Chang, Min Xu, Wei Yuan Yang, Grant J. Jensen
Summary: This study used cryogenic electron tomography to image the nanoscale architecture of cytoskeletal-membrane interactions involved in mitochondrial dynamics in response to damage. The researchers found that, in response to membrane depolarization, mammalian mitochondria predominantly organized into tubular morphology with constrictions, and observed long bundles of actin and septin filaments enriched at these constrictions. They also observed septin-microtube interactions, suggesting the guidance of these two filaments in the cytosolic space. This study provides new insight into the ultrastructural arrangement of molecular components that mediate mitochondrial membrane constriction.
BIOPHYSICAL JOURNAL
(2023)
Article
Biology
Hyun-Sook Park, Eirini Papanastasi, Gabriela Blanchard, Elena Chiticariu, Daniel Bachmann, Markus Plomann, Fanny Morice-Picard, Pierre Vabres, Asma Smahi, Marcel Huber, Christine Pich, Daniel Hohl
Summary: ARP-T1 mutations cause BDCS characterized by shortened cilia, suggesting a link between skin cancer and ciliopathy features.
COMMUNICATIONS BIOLOGY
(2021)
Review
Cell Biology
Bo Wang, Zheyong Liang, Peijun Liu
Summary: This article reviews the role of the primary cilium in cancer, including its architecture, signaling pathways, cilia assembly and disassembly regulators, summarizing new findings in tumor microenvironments and different cancers, highlighting novel possibilities for therapeutic targets in cancer.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Cell Biology
Martin Fischer, Dominik Frank, Reinhild Roesler, Nils Johnsson, Thomas Gronemeyer
Summary: Septins are a part of the cell cytoskeleton and can polymerize into heterogeneous filament structures. The roles of GTP binding and hydrolysis in filament formation and dynamics are not well understood. This study focuses on the subunit composition of human septins, the contribution of different subunits to filament formation, and the kinetics of nucleotide uptake and exchange.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Morgan L. Pimm, Xinbei Liu, Farzana Tuli, Jennifer Heritz, Ashley Lojko, Jessica L. Henty-Ridilla
Summary: PFN1 is an important protein that regulates actin and microtubule assembly, affecting cell division, motility, and morphology. Two genetically encoded versions of tagged PFN1 have been developed and shown to behave identically to the tag-free protein. These tagged PFN1s are reliable tools for studying the interactions of PFN1 with actin or microtubules.
Review
Cell Biology
Julie Stoufflet, Isabelle Caille
Summary: The primary cilium plays an important role in regulating cell motility, especially in neuronal migration, by controlling the rhythm and speed of migration.
Article
Multidisciplinary Sciences
Nikolas Hundt, Daniel Cole, Max F. Hantke, Jack J. Miller, Weston B. Struwe, Philipp Kukura
Summary: This study uses mass photometry to investigate the polymerization process of actin and finds that the traditional nucleation-based models cannot explain the observed distribution of actin oligomers. Instead, the key step of filament formation is a slow transition between different states of an actin filament mediated by cation exchange or ATP hydrolysis. These findings have important implications for understanding the mechanism of actin nucleation and studying protein assembly at the molecular level.
Article
Multidisciplinary Sciences
Kaitlin Katsura, Yukiko Nakano, Yan Zhang, Rozana Shemirani, Wu Li, Pamela Den Besten
Summary: Tooth enamel formation is a complex process regulated by multiple differentiation stages and key genes. WDR72, a gene found in various organs, including the teeth, has been discovered to cause enamel defects when deleted or mutated. Unlike other enamel regulation genes, WDR72 functions intracellularly and regulates endocytosis of proteins. The study suggests that WDR72 plays a role in microtubule assembly and directs membrane mobilization and vesicle transport, providing insights into tissue mineralization.
SCIENTIFIC REPORTS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Michael J. Deeks
Summary: The study highlights the importance of microbe-plant cell interactions in shaping plant cell morphology and function, particularly demonstrating how a specialized formin protein facilitates nitrogen-fixing bacteria colonization in legumes.
Article
Cell Biology
Hoan Van Ngo, Stevens Robertin, Dominik Brokatzky, Magdalena K. Bielecka, Damian Lobato-Marquez, Vincenzo Torraca, Serge Mostowy
Summary: Apoptosis is a crucial mechanism that regulates cell death, and septins are important components that promote mitochondrial apoptosis and combat bacterial infection.
Article
Biochemistry & Molecular Biology
Kerstin Nagel-Wolfrum, Benjamin R. Fadl, Mirjana M. Becker, Kirsten A. Wunderlich, Jessica Schaefer, Daniel Sturm, Jacques Fritze, Burcu Guer, Lew Kaplan, Tommaso Andreani, Tobias Goldmann, Matthew Brooks, Margaret R. Starostik, Anagha Lokhande, Melissa Apel, Karl R. Fath, Katarina Stingl, Susanne Kohl, Margaret M. DeAngelis, Ursula Schlotzer-Schrehardt, Ivana K. Kim, Leah A. Owen, Jan M. Vetter, Norbert Pfeiffer, Miguel A. Andrade-Navarro, Antje Grosche, Anand Swaroop, Uwe Wolfrum
Summary: Usher syndrome (USH) is a common genetic disorder causing deaf-blindness. This study explores the role of harmonin protein in the pathophysiology of USH1C in the human eye. The localization and expression of harmonin in various retinal cells are correlated with the clinical phenotype observed in USH1C patients. Additionally, the study shows the potential of using harmonin_a1 transcript isoform for gene therapy treatment in USH1C patients.
HUMAN MOLECULAR GENETICS
(2023)
Article
Pharmacology & Pharmacy
Baran E. Gueler, Joshua Linnert, Uwe Wolfrum
Summary: VLGR1/ADGRV1 is a large adhesion G protein-coupled receptor associated with Usher syndrome, epilepsy, and other diseases. It is expressed widely in the CNS, eye, and inner ear. Previous research has shown that VLGR1 plays a role in focal adhesion dynamics and cell migration. This study aimed to elucidate the mechanisms of VLGR1 in focal adhesion turnover.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Joshua Linnert, Baran E. Gueler, Jacek Krzysko, Uwe Wolfrum
Summary: VLGR1/ADGRV1 is the largest known adhesion G protein-coupled receptor, and mutations in VLGR1/ADGRV1 are associated with Usher syndrome and epilepsy. This study identified autophagosomes as potential interacting proteins of VLGR1 and revealed the molecular and functional interaction between VLGR1 and key components of the autophagy process. These findings provide insights into the pathomechanisms underlying human USH and epilepsy related to VLGR1 defects.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Cell Biology
Vincenzo Torraca, Magdalena K. Bielecka, Margarida C. Gomes, Dominik Brokatzky, Elisabeth M. Busch-Nentwich, Serge Mostowy
Summary: This study characterized null mutants for zebrafish Sept6 and Sept15 and found that they both play important roles in zebrafish development and host defence against Shigella infection. The mutation of Sept6 and Sept15 did not significantly affect the expression of other zebrafish septin genes.
Editorial Material
Cell Biology
Serge Mostowy, Aurelie Bertin, Helge Ewers
Article
Cell Biology
Arthu Lensen, Margarida C. Gomes, Ana Teresa Lopez-Jimenez, Serge Mostowy
Summary: Shigella, a gram-negative bacterial pathogen, is responsible for bacillary dysentery. The lack of a licensed vaccine and the emergence of antibiotic resistance have made Shigella a priority pathogen requiring urgent attention. In this study, a Shigella-zebrafish infection model and high-content microscopy were used to develop an automated microscopy workflow to study bacterial and neutrophil interactions in vivo. Antibiotics were found to reduce bacterial burden but not neutrophil recruitment, and nalidixic acid was shown to work with leukocytes to control Shigella infection and restrict its dissemination. The researchers propose that their automated microscopy workflow can be useful in innovating infection control treatments in humans.
DISEASE MODELS & MECHANISMS
(2023)
Editorial Material
Cell Biology
Gizem Ozbaykal Guler, Serge Mostowy
Summary: Septins are a conserved protein family that form hetero-oligomeric complexes and assemble into filaments and higher-order structures. Studies by Martins et al. and Cannon et al. reveal that the composition of heteromers affects the physiological role of septin filaments in yeast and human cells.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Cell Biology
Damian Lobato-Marquez, Jose Javier Conesa, Ana Teresa Lopez-Jimenez, Michael E. Divine, Jonathan N. Pruneda, Serge Mostowy
Summary: During Shigella invasion of host cells, it escapes to the cytosol and uses actin polymerization to spread between cells. Host cells employ cell-autonomous immune responses, including autophagy and septin cage entrapment, to restrict this spread. This study used cryo-SXT and other imaging techniques to investigate the interaction between septins, autophagy, and Shigella. The findings provide insights into the targeting of septin-caged Shigella for autophagy and the interaction between autophagy and the cytoskeleton.
JOURNAL OF CELL SCIENCE
(2023)
Article
Microbiology
Sydney L. L. Miles, Vincenzo Torraca, Zoe A. A. Dyson, Ana Teresa Lopez-Jimenez, Ebenezer Foster-Nyarko, Damian Lobato-Marquez, Claire Jenkins, Kathryn E. E. Holt, Serge Mostowy
Summary: By analyzing the genetic sequences of ST99 E. coli, we found that there are two subsets of strains, one with a virulence plasmid pINV and one without. The results of zebrafish infection experiments show that the virulence of ST99 E. coli is temperature-dependent. Furthermore, it was discovered that ST99 strains may have been virulent before the acquisition of pINV, indicating the importance of pINV in the dissemination of ST99 E. coli.
Article
Biochemical Research Methods
Yang W. Huan, Vincenzo Torraca, Russell Brown, Jidapha Fa-arun, Sydney L. Miles, Diego A. Oyarzun, Serge Mostowy, Baojun Wang
Summary: The discovery of CRISPR-Cas9 provides opportunities to selectively kill specific bacteria, but its delivery into bacterial cells is inefficient. In this study, the P1-derived phagemid is used to efficiently deliver the CRISPR-Cas9 chromosomal-targeting system into Escherichia coli and Shigella flexneri, achieving DNA sequence-specific killing of targeted bacterial cells. The P1 phage particles can also deliver cas9 phagemids into S. flexneri in vivo, reducing bacterial load and promoting host survival. This study demonstrates the potential of combining P1 phage-based delivery with the CRISPR system for efficient clearance of bacterial infection.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Cell Biology
Joshua Linnert, Barbara Knapp, Baran E. Gueler, Karsten Boldt, Marius Ueffing, Uwe Wolfrum
Summary: The human Usher syndrome is characterized by progressive vision and hearing loss. Mutations in ADGRV1 and CIB2 genes are associated with two sub-types of Usher syndrome. The proteins encoded by these two genes belong to distinct protein families. The cellular functions of ADGRV1 and CIB2 are still unclear, but they are found to interact with each other and play a role in primary cilia function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Jessica Schaefer, Nicole Wenck, Katharina Janik, Joshua Linnert, Katarina Stingl, Susanne Kohl, Kerstin Nagel-Wolfrum, Uwe Wolfrum
Summary: Human Usher syndrome (USH) is a complex genetic disorder that causes combined deafness and blindness. The underlying mechanisms of the disease, particularly in the eye and retina, are not well understood. This study identifies a role for the scaffold protein harmonin, encoded by the USH1C gene, in regulating the canonical Wnt/beta-catenin signaling pathway. The findings suggest that USH1C/harmonin acts as a suppressor of the pathway, and dysregulation of this pathway may contribute to the development of USH.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Immunology
Vincenzo Torraca, Dominik Brokatzky, Sydney L. Miles, Charlotte E. Chong, P. Malaka De Silva, Stephen Baker, Claire Jenkins, Kathryn E. Holt, Kate S. Baker, Serge Mostowy
Summary: Shigella, including specific serotypes, can establish persistent infection in the zebrafish model. The O-antigen plays a crucial role in this process, and the serotype-associated effects observed in humans are also observed in zebrafish.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Hematology
Sammy El-Mansi, Christopher L. Robinson, Katja B. Kostelnik, Jessica J. McCormack, Tom P. Mitchell, Damian Lobato-Marquez, Vinothini Rajeeve, Pedro Cutillas, Daniel F. Cutler, Serge Mostowy, Thomas D. Nightingale
Summary: In response to tissue injury, the ultra-large glycoprotein von Willebrand factor (VWF) is released from endothelial storage organelles into the blood vasculature, leading to platelet recruitment. Endothelial cells have developed mechanisms, such as an actomyosin ring, to overcome the challenge of releasing VWF. Inhibiting the formation or function of these structures could be a potential therapeutic target for thrombotic diseases.