Article
Multidisciplinary Sciences
Tomasz Zielinski, Joanna Pabijan, Bartlomiej Zapotoczny, Joanna Zemla, Julita Wesolowska, Joanna Pera, Malgorzata Lekka
Summary: In this study, the researchers used atomic force microscopy to measure the changes in biomechanical properties of neuroblastoma SH-SY5Y cells under oxygen and glucose deprivation and reoxygenation conditions. The results showed that the metabolic activity of the cells decreased with longer periods of oxygen and glucose deprivation, and the cells became softer. However, the mechanical properties of the cells recovered after reoxygenation. These changes in the nanomechanical properties were attributed to the remodelling of actin filaments.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Jamis McGrath, Chun-Yu Tung, Xiayi Liao, Inna A. Belyantseva, Pallabi Roy, Oisorjo Chakraborty, Jinan Li, Nicolas F. Berbari, Christian C. Faaborg-Andersen, Melanie Barzik, Jonathan E. Bird, Bo Zhao, Lata Balakrishnan, Thomas B. Friedman, Benjamin J. Perrin
Summary: Research indicates that actin turnover is increased at the tips of mechanotransducing stereocilia during bundle maturation. These data show that actin is remodeled, likely by a severing mechanism, in response to mechanotransduction.
Article
Biochemistry & Molecular Biology
Hugo Wioland, Stephane Fremont, Berengere Guichard, Arnaud Echard, Antoine Jegou, Guillaume Romet-Lemonne
Summary: MICAL1-mediated oxidation of actin filaments amplifies cofilin severing action, bypassing the need for cofilin activation. Direct post-translational oxidation modification of actin filaments in cells triggers their disassembly.
Article
Biochemistry & Molecular Biology
Sharad V. Jaswandkar, Kalpana S. Katti, Dinesh R. Katti
Summary: This study investigates the impact of ADF/cofilin on actin filaments using molecular dynamics simulations. The results show that the binding of ADF/cofilin modifies the conformation and alignment of actin filaments locally, leading to filament severing at the boundaries. The findings provide important insights into the cofilin-mediated actin dynamics.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Multidisciplinary Sciences
Weiji Weng, Xiaokun Gu, Yang Yang, Qiao Zhang, Qi Deng, Jie Zhou, Jinke Cheng, Michael X. Zhu, Junfeng Feng, Ou Huang, Yong Li
Summary: SUMOylation plays a key role in modulating protein function. Here, the authors uncover a form of SUMOylation, termed N-αSUMOylation, where SUMO1 attaches to the N-terminus of cofilin1. This SUMOylation promotes cofilin-1 binding to F-actin and cofilin-induced actin depolymerization.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Ryan K. Hylton, Jessica E. Heebner, Michael A. Grillo, Matthew T. Swulius
Summary: In this study, the authors demonstrate that filopodial actin filaments switch between bundles of fascin-crosslinked actin and cofilin-decorated filaments. The authors also observe that cofilactin is associated with various dynamic events within filopodia. Furthermore, the hyper-twisting of actin due to cofilin binding leads to a rearrangement of filament packing, which excludes fascin from the base of filopodia.
NATURE COMMUNICATIONS
(2022)
Article
Plant Sciences
Yuxiang Jiang, Qiaonan Lu, Shanjin Huang
Summary: ADF7 and ADF10 have distinct functions in regulating actin turnover, with ADF7 exhibiting lower affinity for ADP-G-actin and less efficiency in severing and depolymerizing actin filaments. Additionally, ADF7 shows broader distribution in pollen grains and has different intracellular localization compared to ADF10.
Article
Multidisciplinary Sciences
Tommi Kotila, Hugo Wioland, Muniyandi Selvaraj, Konstantin Kogan, Lina Antenucci, Antoine Jegou, Juha T. Huiskonen, Guillaume Romet-Lemonne, Pekka Lappalainen
Summary: The authors report the structure and function analysis of highly divergent actin from Leishmania parasite. The study reveals the rapid dynamics and molecular basis of parasite actin, providing insight into the evolution of the actin cytoskeleton. The findings show how divergent parasites achieve rapid actin dynamics using a simple set of actin-binding proteins, elucidating the evolution of the actin cytoskeleton.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Kohki Takayama, Kota Matsuda, Hiroshi Abe
Summary: This study constructed actin-cofilin rods in vitro using a physiological buffer containing methylcellulose and found that these rods have specific shapes and structures. The formation and evolution processes of these rods under different conditions were also explored, providing important clues for understanding the functions and regulatory mechanisms of cytoplasmic actin-cofilin rods.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biology
Yichen Sun, Moyi Li, Junhua Geng, Sibie Meng, Renjun Tu, Yan Zhuang, Mingkuan Sun, Menglong Rui, Mengzhu Ou, Guangling Xing, Travis K. Johnson, Wei Xie
Summary: Neuroligins, through an interaction between DNlg2 and RACK1, regulate F-Actin assembly at the Drosophila NMJ via the Cofilin signaling pathway. Deletion of DNlg2 disrupts the actin cytoskeleton and results in abnormal synaptic transmission and locomotion. Overexpression of certain forms of Cofilin can rescue these defects. These findings highlight the importance and complexity of Neuroligins in neural connectivity.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biology
Yichen Sun, Moyi Li, Junhua Geng, Sibie Meng, Renjun Tu, Yan Zhuang, Mingkuan Sun, Menglong Rui, Mengzhu Ou, Guangling Xing, Travis K. Johnson, Wei Xie
Summary: Neuroligins are cell adhesion proteins with genetic links to autism spectrum disorders. They regulate F-Actin assembly through the RACK1-Cofilin signaling pathway to control synaptic morphology and function at neuromuscular junctions.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Lena Hoffmann, Marcel S. Waclawczyk, Stephan Tang, Eva-Maria Hanschmann, Manuela Gellert, Marco B. Rust, Carsten Culmsee
Summary: This study demonstrates that the actin-regulating protein cofilin1 plays a crucial role in oxidative neuronal death by affecting mitochondrial function and oxidation. Additionally, cofilin1 can influence cellular metabolic pathways and resistance to oxidative stress.
CELL DEATH & DISEASE
(2021)
Article
Microbiology
T. Essock-Burns, B. D. Bennett, D. Arencibia, S. Moriano-Gutierrez, M. Medeiros, M. J. McFall-Ngai, E. G. Ruby
Summary: This study demonstrates that quorum-sensing regulation by the Vibrio fischeri population induces a tissue phenotype that promotes the retention of this extracellular symbiont within the light organ of its host. Actin polymerization is identified as the primary mechanism underlying constriction, and host responses to the presence of symbionts change as a function of tissue maturation.
Article
Cell Biology
Shashank Shekhar, Gregory J. Hoeprich, Jeff Gelles, Bruce L. Goode
Summary: This study shows that twinfilin, a member of the ADF-homology family, induces depolymerization of ADP-Pi barbed ends even under assembly-promoting conditions, bypassing filament aging prerequisites and promoting disassembly of newly polymerized actin filaments.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Heidi Ulrichs, Ignas Gaska, Shashank Shekhar
Summary: Cells regulate actin assembly by controlling reactions at actin filament barbed ends. Three proteins, formin, CP, and twinfilin, have distinct roles at these barbed ends. Using microfluidics-assisted TIRF microscopy, it was found that all three proteins can bind filament barbed ends simultaneously. Single-molecule experiments showed that twinfilin cannot bind barbed ends occupied by formin in the presence of CP. This study establishes a paradigm where polymerases, depolymerases, and cappers together tune actin assembly.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Sri HariKrishna Vellanki, Rodrigo G. B. Cruz, Hanne Jahns, Lance Hudson, Giovanni Sette, Adriana Eramo, Ann M. Hopkins
Article
Oncology
Sri Harikrishna Vellanki, Rodrigo G. B. Cruz, Cathy E. Richards, Yvonne E. Smith, Lance Hudson, Hanne Jahns, Ann M. Hopkins
ANTICANCER RESEARCH
(2019)
Article
Radiology, Nuclear Medicine & Medical Imaging
Sena Tuncer, Sherif Mehralivand, Stephanie A. Harmon, Thomas Sanford, G. Thomas Brown, Lindsay S. Rowe, Maria J. Merino, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke, Baris Turkbey
ABDOMINAL RADIOLOGY
(2020)
Article
Medicine, General & Internal
Sara Charmsaz, Ben Doherty, Sinead Cocchiglia, Damir Vareslija, Attilio Marino, Nicola Cosgrove, Ricardo Marques, Nolan Priedigkeit, Siobhan Purcell, Fiona Bane, Jarlath Bolger, Christopher Byrne, Philip J. O'Halloran, Francesca Brett, Katherine Sheehan, Kieran Brennan, Ann M. Hopkins, Stephen Keelan, Petra Jagust, Stephen Madden, Chiara Martinelli, Matteo Battaglini, Steffi Oesterreich, Adrian V. Lee, Gianni Ciofani, Arnold D. K. Hill, Leonie S. Young
Article
Oncology
Rodrigo G. B. Cruz, Stephen F. Madden, Cathy E. Richards, Sri HariKrishna Vellanki, Hanne Jahns, Lance Hudson, Joanna Fay, Naoimh O'Farrell, Katherine Sheehan, Karin Jirstrom, Kieran Brennan, Ann M. Hopkins
Summary: The study reveals that JAM-A regulates HER3 expression levels through the pathway involving beta-catenin and FOXA1, thereby reducing HER3-dependent tumorigenic signaling. This discovery may serve as a novel drug target for overcoming resistance to HER2-targeted therapies in breast cancer.
Article
Oncology
Cathy E. Richards, Katherine M. Sheehan, Elaine W. Kay, Charlotta Hedner, David Borg, Joanna Fay, Anthony O'Grady, Arnold D. K. Hill, Karin Jirstrom, Ann M. Hopkins
Summary: High levels of Junctional Adhesion Molecule-A (JAM-A) protein have been associated with aggressive disease in various cancers, particularly in breast cancer patients overexpressing HER2. The study aimed to investigate the link between JAM-A and HER2 levels in gastro-esophageal (GE) cancers, revealing a significant correlation when accounting for intra-tumoral heterogeneity. This highlights the importance of considering heterogeneity in cancer biomarker studies for the benefit of patient treatment.
Article
Cell Biology
Viktorija Juric, Lance Hudson, Joanna Fay, Cathy E. Richards, Hanne Jahns, Maite Verreault, Franck Bielle, Ahmed Idbaih, Martine L. M. Lamfers, Ann M. Hopkins, Markus Rehm, Brona M. Murphy
Summary: The activation of CDKs contributes to the uncontrolled proliferation of tumor cells, such as in the case of GBM. In this study, two CDK inhibitors, CYC065 and THZ1, showed promising therapeutic efficacy in GBM patient-derived cell lines, suppressing invasion and inducing cell death. These novel CKIs have the potential to be further investigated for clinical applications in the treatment of GBM.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Rodrigo G. B. Cruz, Stephen F. Madden, Kieran Brennan, Ann M. Hopkins
Summary: JAM-A transcriptionally regulates the expression of HER2 via FOXA1, and is associated with survival outcomes in patients with HER2-positive breast or gastric tumors.
Article
Biochemistry & Molecular Biology
Laura T. Fee, Debananda Gogoi, Michael E. O'Brien, Emer McHugh, Michelle Casey, Ciara Gough, Mark Murphy, Ann M. Hopkins, Tomas P. Carroll, Noel G. McElvaney, Emer P. Reeves
Summary: Alpha-1 antitrypsin deficiency (AATD) is associated with increased risk of emphysema, COPD, vasculitis, and impaired wound healing. Dysregulated complement activation in AATD leads to elevated levels of C3d, which triggers degranulation of neutrophils and inhibits endothelial cell migration and wound healing. This study highlights potential implications for AATD-related vasculitis.
Article
Oncology
Yvonne E. Smith, Guannan Wang, Ciara L. Flynn, Stephen F. Madden, Owen MacEneaney, Rodrigo G. B. Cruz, Cathy E. Richards, Hanne Jahns, Marian Brennan, Mattia Cremona, Bryan T. Hennessy, Katherine Sheehan, Alexander Casucci, Faizah A. Sani, Lance Hudson, Joanna Fay, Sri H. Vellanki, Siobhan O'Flaherty, Marc Devocelle, Arnold D. K. Hill, Kieran Brennan, Saraswati Sukumar, Ann M. Hopkins
Summary: Specific drug targets for breast ductal carcinoma in situ (DCIS) are difficult to determine, but this study suggests that JAM-A, a cell surface protein, could be a potential therapeutic target in DCIS patients. The study found that JAM-A is upregulated in DCIS patient tissues and a novel JAM-A-binding peptide inhibitor showed efficacy in inhibiting tumor growth in in vivo models. This finding provides valuable insights for the development of novel treatments for DCIS patients.
Article
Pathology
Sushant Patkar, Jessica Beck, Stephanie Harmon, Christina Mazcko, Baris Turkbey, Peter Choyke, G. Thomas Brown, Amy LeBlanc
Summary: A convolutional neural network was trained to classify histologic patterns of osteosarcomas in humans using data from canine osteosarcomas. The trained model achieved good results and was able to identify distinct clinical responses in canine osteosarcomas.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Oncology
David Milewski, Hyun Jung, G. Thomas Brown, Yanling Liu, Ben Somerville, Curtis Lisle, Marc Ladanyi, Erin R. Rudzinski, Hyoyoung Choo-Wosoba, Donald A. Barkauskas, Tammy Lo, David Hall, Corinne M. Linardic, Jun S. Wei, Hsien-Chao Chou, Stephen X. Skapek, Rajkumar Venkatramani, Peter K. Bode, Seth M. Steinberg, George Zaki, Igor B. Kuznetsov, Douglas S. Hawkins, Jack F. Shern, Jack Collins, Javed Khan
Summary: This study utilized convolutional neural networks (CNN) to predict high-risk mutations and prognosis of rhabdomyosarcoma (RMS) based on histologic features learned from H&E images. The CNN model achieved superior performance in predicting survival and event-free outcomes compared to current molecular-clinical risk stratification methods.
CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Anu Prakash, Shishir Paunikar, Mark Webber, Emma Mcdermott, Sri H. Vellanki, Kerry Thompson, Peter Dockery, Hanne Jahns, James A. L. Brown, Ann M. Hopkins, Emer Bourke
Summary: This study investigates the mechanistic contributions of centrosome amplification (CA) induction alone to tumor architecture and extracellular matrix (ECM) remodeling. The results demonstrate that CA induction can lead to cell migration and invasion, disruption of epithelial cell-cell junction integrity, and dysregulation of cell junction proteins. Furthermore, CA induction increases the expression of integrin beta-3, fibronectin-1, and matrix metalloproteinase enzymes, promoting cell-ECM attachment, ECM degradation, and a migratory and invasive cell phenotype.
JOURNAL OF CELL SCIENCE
(2023)
Meeting Abstract
Surgery
E. J. Rutherford, C. E. Richards, A. O. Leech, A. D. K. Hill, A. M. Hopkins
BRITISH JOURNAL OF SURGERY
(2021)
Meeting Abstract
Oncology
Ann M. Hopkins, Yvonne E. Smith, Guannan Wang, Ciara Flynn, Alexander Casucci, Sri HariKrishna Vellanki, Lance Hudson, Kieran Brennan, Mattia Cremona, Saraswati Sukumar
