Article
Cell Biology
Kathryn N. Becker, Krista M. Pettee, Amanda Sugrue, Kevin A. Reinard, Jason L. Schroeder, Kathryn M. Eisenmann
Summary: Targeting mDia is an effective strategy against invasion and tumor microtube networking, while inhibiting ROCK is contraindicated for treating brain cancer.
Article
Cell Biology
Beatriz Almaran, Guillem Ramis, Silvia Fernandez de Mattos, Priam Villalonga
Summary: In this study, the functional crosstalk between receptor tyrosine kinases (RTKs) and Rho GTPases was analyzed, with a focus on the specific contribution of Rnd3 to the invasive phenotype of glioblastoma cells. RTK inhibition decreased cell motility and invasion, and activated the RhoA/ROCK pathway for actin cytoskeletal reorganization. Rnd3 depletion had similar effects to RTK inhibition, suggesting its crucial role in regulating the invasive phenotype of glioblastoma cells through actin cytoskeletal reorganization.
Article
Immunology
Vitor R. Munoz, Rafael C. Gaspar, Matheus B. Severino, Ana P. A. Macedo, Fernando M. Simabuco, Eduardo R. Ropelle, Dennys E. Cintra, Adelino S. R. da Silva, Young-Bum Kim, Jose Rodrigo Pauli
Summary: Physical exercise can restore the levels of RhoA and ROCK2 proteins in the skeletal muscle of obese animals, increase phosphorylation of IRS1 and Akt proteins, and decrease levels of inhibitory regulators such as PTEN and PTP-1B. These findings suggest that exercise-induced upregulation of the RhoA-ROCK2 signaling pathway in skeletal muscle is associated with improved systemic insulin sensitivity in obese mice.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Antonina Alexandrova, Maria Lomakina
Summary: Tumor shrinkage is not the only indicator of treatment success, as cancer progression and metastasis formation play crucial roles. The plasticity of tumor cells in switching between different migration modes contributes to their ability to avoid treatment. Identifying specific markers for migratory plasticity is important for successful treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Jessica Wayt, Alexander Cartagena-Rivera, Dipannita Dutta, Julie G. Donaldson, Clare M. Waterman
Summary: The Rho-associated kinase ROCK2 is required for clathrin-independent endocytosis (CIE) of MHCI and CD59 by promoting myosin II activity. Myosin IIA and IIB drive internalization of specific cargoes in different cellular locations, mediating spatial regulation of CIE.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Biochemistry & Molecular Biology
David Sebastian Hernandez-Toledano, Libia Vega
Summary: The non-cholinergic molecular targets of organophosphate compounds, including malathion and its dialkylphosphate metabolites, have been shown to affect the cytoskeleton components and organization of cells. These compounds induce changes in actin and tubulin polymerization, leading to morphological alterations and increased cell migration. The activation of cytoskeletal regulators, such as Cdc42, plays a key role in these effects. Understanding the non-cholinergic targets of organophosphates is important in elucidating their role in the development of non-neurological diseases.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Multidisciplinary Sciences
Robert A. Law, Alexander Kiepas, Habben E. Desta, Emiliano Perez Ipina, Maria Parlani, Se Jong Lee, Christopher L. Yankaskas, Runchen Zhao, Panagiotis Mistriotis, Nianchao Wang, Zhizhan Gu, Petr Kalab, Peter Friedl, Brian A. Camley, Konstantinos Konstantopoulos
Summary: Cells regulate epithelial integrity and cancer metastasis through adherens junction dynamics. This study shows that the spatial confinement of peritumor stroma promotes metastatic cell dissemination by disrupting cell-cell adhesion. The mechanism involves myosin IIA dismantling E-cadherin junctions, which is controlled by RhoA/ROCK activation mediated by nucleocytoplasmic shuttling of RacGAP1 and Ect2 and increased microtubule dynamics.
Article
Multidisciplinary Sciences
Amalia Hadjitheodorou, George R. R. Bell, Felix Ellett, Shashank Shastry, Daniel Irimia, Sean R. Collins, Julie A. Theriot
Summary: Neutrophils migrate with stable front-rear polarization, and myosin II plays a role in promoting this stability by suppressing receptor inputs at the cell rear. Subcellular optogenetic receptor activation can reorient weakly polarized cells but is refractory to strongly polarized cells, indicating that the cell rear's sensitivity to receptor input is key for directional reversal. Additionally, the RhoA/ROCK/myosin II pathway limits the ability of receptor inputs to signal to Cdc42 in reprogramming migrating neutrophils.
NATURE COMMUNICATIONS
(2021)
Review
Cell Biology
Maria-Graciela Delgado, Ana-Maria Lennon-Dumenil
Summary: Migration of immune cells is crucial for building an efficient defense system, playing important roles from early development to tissue patrolling and lymph node migration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katja Scharinger, Sebastian Maxeiner, Carmen Schalla, Stephan Rutten, Martin Zenke, Antonio Sechi
Summary: The bimolecular complex between LSP1 and myosin1e plays a crucial role in regulating actin cytoskeleton remodeling and focal adhesion dynamics in macrophages, impacting cell migration, lamellipodia formation, and focal adhesion turnover.
Article
Endocrinology & Metabolism
Siva S. V. P. Sakamuri, Venkata N. Sure, Lokanatha Oruganti, William Wisen, Partha K. Chandra, Ning Liu, Vivian A. Fonseca, Xiaoying Wang, Jennifer Klein, Prasad V. G. Katakam
Summary: Hypoglycemia affects the proteome of brain microvessels, potentially impairing cellular cytoskeleton and RNA processing.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Review
Biochemistry & Molecular Biology
Vera B. Dugina, Galina S. Shagieva, Anton S. Shakhov, Irina B. Alieva
Summary: Endothelial cells (EC) line the inner surface of vessels and regulate vascular permeability, with their actin cytoskeleton crucial for maintaining endothelial barrier function. Non-muscle cells express two actin isoforms, beta and gamma, which have different roles in cell survival, cell division, and neoplastic transformation depending on the cell type. The spatial organization of cytoplasmic actins in different cell types, particularly in endothelial cells, is closely linked to their functional activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Maria S. Shutova, Julia Borowczyk, Barbara Russo, Sihem Sellami, Justyna Drukala, Michal Wolnicki, Nicolo C. Brembilla, Gurkan Kaya, Andrei I. Ivanov, Wolf-Henning Boehncke
Summary: Abnormal mechanotransduction and compromised epithelial barrier function are observed in various human pathologies, including inflammatory skin disorders. This study investigates the cytoskeletal mechanisms involved in the regulation of inflammatory responses in the epidermis. The results suggest that inflammation up-regulates the Rho-myosin II pathway and disrupts adherens junctions, leading to YAP nuclear entry. The disruption of adherens junctions, increased paracellular permeability, and YAP nuclear translocation are regulated by ROCK2 independently of myosin II activation. The inhibitor KD025 demonstrates the effects of ROCK2 on the inflammatory response in the epidermis through cytoskeletal and transcription-dependent mechanisms.
Article
Chemistry, Medicinal
Zilun Hu, Doree Sitkoff, Peter W. Glunz, Yan Zou, Cailan Wang, Jodi K. Muckelbauer, Leonard P. Adam, Ruth R. Wexler, Mimi L. Quan
Summary: Derivatives of lactam, cyclic urea, and carbamate were investigated as replacements for aniline amide in a series of phthalazinone-based ROCK inhibitors. Potent ROCK2 inhibitors, such as compound 22, were identified, demonstrating excellent overall kinase selectivity and good isoform selectivity over ROCK1.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Genetics & Heredity
Guangzhao Guan, Richard D. D. Cannon, Dawn E. E. Coates, Li Mei
Summary: The mechanical properties of cells play an important role in tissue homeostasis and various cellular processes. These properties are determined by the cytoskeleton, which is a complex and dynamic network of microfilaments, intermediate filaments, and microtubules. The Rho-kinase/ROCK signaling pathway regulates the architecture of this cytoskeletal network, influencing cell behavior.
Article
Biophysics
Martin Rausch, David Boehringer, Martin Steinmann, Dirk W. Schubert, Stefan Schruefer, Christoph Mark, Ben Fabry
BIOPHYSICAL JOURNAL
(2020)
Article
Biophysics
Delf Kah, Christopher Duerrbeck, Werner Schneider, Ben Fabry, Richard Carl Gerum
BIOPHYSICAL JOURNAL
(2020)
Article
Ophthalmology
A. Musayeva, A. Gericke, F. Jaeger, F. Paulsen, M. Braun, B. Fabry, R. Braun, D. Pauly, C. Holtmann, G. Geerling
Summary: The Sicca-Forderpreis, or Dry Eye Award, supports scientific research on the pathogenesis, diagnostics, and treatment of dry eye and ocular surface diseases. Projects funded by this award in 2016 showcased the roles of muscarinic receptors and urea in dry eye pathogenesis, as well as innovative treatment approaches. These projects demonstrate potential for significant developments in understanding and treating dry eye, but their long-term clinical relevance remains to be established.
Article
Multidisciplinary Sciences
Sebastian J. Mueller, Elham Mirzahossein, Emil N. Iftekhar, Christian Baecher, Stefan Schruefer, Dirk W. Schubert, Ben Fabry, Stephan Gekle
Article
Multidisciplinary Sciences
Christoph Mark, Tina Czerwinski, Susanne Roessner, Astrid Mainka, Franziska Hoersch, Lucas Heublein, Alexander Winterl, Sebastian Sanokowski, Sebastian Richter, Nina Bauer, Thomas E. Angelini, Gerold Schuler, Ben Fabry, Caroline J. Voskens
NATURE COMMUNICATIONS
(2020)
Article
Biochemical Research Methods
Andreas Bauer, Magdalena Prechova, Lena Fischer, Ingo Thievessen, Martin Gregor, Ben Fabry
Summary: Cellular force generation and transmission are crucial for biological processes, and the pyTFM tool allows for comprehensive evaluation and analysis of Traction Force Microscopy and Monolayer Stress Microscopy experiments, aiding non-expert users in studying cell mechanics.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Cell Biology
Magdalena Prechova, Zuzana Adamova, Anna-Lena Schweizer, Miloslava Maninova, Andreas Bauer, Delf Kah, Samuel M. Meier-Menches, Gerhard Wiche, Ben Fabry, Martin Gregor
Summary: This study reveals the crucial role of plectin in supporting intercellular junctions through organizing cortical cytoskeletal networks in epithelial sheets. Deficiency of plectin leads to abnormal cytoarchitecture, elevated intracellular tension, and reduced intercellular cohesion, resulting in destabilization of tissues under mechanical stress.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biophysics
Lovis Schween, Norbert Muecke, Stephanie Portet, Wolfgang H. Goldmann, Harald Herrmann, Ben Fabry
Summary: Vimentin is a highly charged intermediate filament protein that undergoes lateral and longitudinal assembly processes, which are accelerated by increasing salt concentration.
BIOPHYSICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Kazunori Sunadome, Alek G. G. Erickson, Delf Kah, Ben Fabry, Csaba Adori, Polina Kameneva, Louis Faure, Shigeaki Kanatani, Marketa Kaucka, Ivar Dehnisch Ellstroem, Marketa Tesarova, Tomas Zikmund, Jozef Kaiser, Steven Edwards, Koichiro Maki, Taiji Adachi, Takuya Yamamoto, Kaj Fried, Igor Adameyko
Summary: The developing skeleton produces mechanical tension that guides the directional outgrowth of skeletal muscles. Formation of oriented myofibrils is crucial in musculoskeletal development. The mechanisms that control myocyte orientation and fusion for muscle directionality in adults are still unknown.
NATURE COMMUNICATIONS
(2023)
Article
Physics, Applied
Sebastian J. Mueller, Ben Fabry, Stephan Gekle
Summary: Bioprinting of living cells can lead to shape deformations, affecting cell survival and functionality. Extensional stresses occurring when cells leave the nozzle have been ignored. Lattice Boltzmann simulations and a finite-element based cell model were used to study cell deformation inside the nozzle and at its exit. Two simple methods were developed to predict maximum cell stress and approximate cell strains based on printing parameters.
PHYSICAL REVIEW APPLIED
(2023)
Article
Engineering, Electrical & Electronic
Delf Kah, Alexander Winterl, Magdalena Prechova, Ulrike Schoeler, Werner Schneider, Oliver Friedrich, Martin Gregor, Ben Fabry
Summary: The cell stretcher is a device used to simulate dynamic mechanical loading conditions and study cellular responses, suitable for biological research. Controlled by open-source software, the cell stretcher can stretch multiple substrates simultaneously, allowing for studies including microscopic image analysis. Research shows that the cell stretcher is suitable for studying complex mechano-biological processes.
Meeting Abstract
Dermatology
C. Mark, T. Czerwinksi, S. Roessner, A. Mainka, F. Hoersch, L. Heublein, A. Winterl, S. Sanokowski, S. Richter, N. Bauer, T. Angelini, G. Schuler, B. Fabry, C. Bosch-Voskens
JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT
(2020)
Meeting Abstract
Biophysics
David Boehringer, Martin Rausch, Martin Steinmann, Stefan Schruefer, Dirk W. Schubert, Annamaria Haertl, Christoph Mark, Ben Fabry
BIOPHYSICAL JOURNAL
(2020)
Meeting Abstract
Biophysics
David Boehringer, Christoph Mark, Nadine Grummel, Pamela L. Strissel, Reiner Strick, Thomas J. Grundy, Geraldine M. O'Neill, Ben Fabry
BIOPHYSICAL JOURNAL
(2020)
Meeting Abstract
Biophysics
Tina Czerwinski, Christoph Mark, Susanne Roessner, Caroline Bosch-Voskens, Tapomoy Bhattacharjee, Thomas E. Angelini, Ben Fabry
BIOPHYSICAL JOURNAL
(2020)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)