Commentary on: The actin bundling activity of ITPKA mainly accounts for its migration-promoting effect in lung cancer cells DOI Creative Commons
Xin Zhang,

Jiadi He,

Dong Ren

et al.

Bioscience Reports, Journal Year: 2023, Volume and Issue: 43(9)

Published: Sept. 1, 2023

1,4,5-triphosphate 3-kinase A (ITPKA) was first described and characterized by Irvine et al. in 1986 cloned Takazawa 1990. It is one of the components Ca2+ calmodulin signaling pathway a substrate for cAMP-dependent kinase (PKA) protein C (PKC), mainly involved regulation intracellular inositol polyphosphate molecules. Through series studies, Sabine's team has found that ITPKA expression up-regulated variety cancer cells, silencing inhibited while overexpressing promoted cell migration vitro metastasis vivo. The latest research from demonstrated H1299 lung mechanism which invasion predominantly depending on ability binding to F-actin, will induce cells form tight flexible actin networks. Small molecule compounds targeting IP3 activity may only inhibit caused enhanced under ATP stimulation, but not cytoskeletal remodeling F-actin driven cells. Therefore, targeted therapeutic strategy focusing blocking indispensable when designing inhibitors protein.

Language: Английский

From actin waves to mechanism and back: How theory aids biological understanding DOI Creative Commons
Carsten Beta, Leah Edelstein‐Keshet, Nir S. Gov

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 10, 2023

Actin dynamics in cell motility, division, and phagocytosis is regulated by complex factors with multiple feedback loops, often leading to emergent dynamic patterns the form of propagating waves actin polymerization activity that are poorly understood. Many wave community have attempted discern underlying mechanisms using experiments and/or mathematical models theory. Here, we survey methods hypotheses for based on signaling networks, mechano-chemical effects, transport characteristics, examples drawn from Dictyostelium discoideum, human neutrophils, Caenorhabditis elegans, Xenopus laevis oocytes. While experimentalists focus details molecular components, theorists pose a central question universality: Are there generic, model-independent, principles, or just boundless cell-specific details? We argue equally important understanding emergence, evolution, persistence conclude few challenges future studies.

Language: Английский

Citations

26
Kinetic trapping organizes actin filaments within liquid-like protein droplets DOI Creative Commons
Aravind Chandrasekaran, Kristin Graham, Jeanne C. Stachowiak

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 11, 2024

Abstract Several actin-binding proteins (ABPs) phase separate to form condensates capable of curating the actin network shapes. Here, we use computational modeling understand principles organization within VASP condensate droplets. Our simulations reveal that different shapes, namely shells, rings, and mixture states are highly dependent on kinetics VASP-actin interactions, suggesting they arise from kinetic trapping. Specifically, show reducing residence time filaments reduces degree bundling, thereby promoting assembly shells rather than rings. We validate model predictions experimentally using a VASP-mutant with decreased bundling capability. Finally, investigate ring opening deformed droplets found sphere-to-ellipsoid transition is favored under wide range filament lengths while ellipsoid-to-rod only permitted when have specific lengths. findings highlight key mechanisms phase-separated ABPs.

Language: Английский

Citations

6
Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony DOI Creative Commons
Robert Wysocki, Joana Isabel Rodrigues, Ireneusz Litwin

et al.

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(11)

Published: Oct. 30, 2023

Abstract Arsenic and antimony are metalloids with profound effects on biological systems human health. Both elements toxic to cells organisms, exposure is associated several pathological conditions including cancer neurodegenerative disorders. At the same time, arsenic- antimony-containing compounds used in treatment of multiple diseases. Although these can both cause cure disease, their modes molecular action incompletely understood. The past decades have seen major advances our understanding arsenic toxicity, emphasizing genotoxicity proteotoxicity as key contributors pathogenesis. In this review, we highlight mechanisms by which focusing genotoxic proteotoxic effects. maintain proteostasis during metalloid also described. Furthermore, address how metalloid-induced may promote disease be interrelated together contribute proteinopathies. A deeper cellular toxicity response links pathogenesis development strategies for prevention treatment.

Language: Английский

Citations

11
Electrical Forces Improve Memory in Old Age DOI
Colin McCaig

Reviews of physiology, biochemistry and pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 453 - 520

Published: Jan. 1, 2025

Language: Английский

Citations

0
Plasma membrane and nuclear phosphatidylinositol 4,5-bisphosphate signalling in cancer DOI Creative Commons
Agnieszka Chytła, Stephanie Rattay, Baki Akgül

et al.

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Feb. 6, 2025

The development of metastasis is a leading cause cancer-related death that involves specific changes in the plasma membrane (PM) and nucleus cancer cells. Elevated levels lipids, including sphingomyelin, cholesterol, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), PM, contribute to rigidity, lipid raft formation, actin polymerisation dynamics, processes drive cell invasion. This review discusses relationship between well-studied cytoplasmic phosphoinositides their lesser-known nuclear counterparts, highlighting functional role metastatic progression. Nuclear phosphoinositides, particularly PI(4,5)P2, are essential for regulating transcription factors chromatin organisation, thereby shaping gene expression patterns. We also explore PI(4,5)P2 its metabolism invasiveness metastasis, proposing model which dysregulation cytosolic and/or pool triggers malignant transformation. Understanding PI(4,5)P2-related mechanisms underlying may provide insights into potential therapeutic targets, paving way more effective therapies improved patient outcomes.

Language: Английский

Citations

0
Mechanosensitive apoptosis in Alzheimer’s disease DOI Open Access

G.V. Sapozhnikov,

Rajesh Ranganathan, Shoutang Wang

et al.

Ageing and Neurodegenerative Diseases, Journal Year: 2025, Volume and Issue: 5(2)

Published: April 28, 2025

The incidence of neurodegenerative diseases is increasing exponentially, with Alzheimer’s disease (AD) being a notorious example. AD progressive, aging-related, multifactorial disease, and no uniform theory exists regarding its etiology. One hypothesis implicates defects in the organism’s mechanosensing mechanotransduction mechanisms. deleterious effects mechanical stress neurodegeneration have been proven through multiple studies observations, but pathways linking inputs to progression remain unclear. It has proposed that nervous tissue primarily responds sources astrocytes microglia, activation Piezo1 TRPV4 ion channels. An area current research examining might be involved elevated oxidative dysregulated apoptotic pathways. We summarized understanding related AD. Our review indicated relationship between crucial Hippo pathway (MST1 humans) KCNN4 worth following up future studies. noted G3BP1 G3BP2 FlnA-mediated are linked ceramide production, along their interaction granules - key element for onset apoptosis, which assembled, among others, response stress. This sheds light on how input disrupts what implications also identifies potential targets focus.

Language: Английский

Citations

0
Recent advances in nuclear actin research DOI Creative Commons
Anikó Szabó,

Péter Borkúti,

Zoltán Kovács

et al.

Nucleus, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 4, 2025

Actin was first observed in the nucleus more than sixty years ago but research on nuclear actin did not receive significant attention for next forty years. It only started to accelerate around year 2000, when convincing experimental data emerged indicating that participates essential processes. Today, we know is involved transcription, replication, DNA repair, chromatin remodeling, and determination of shape size. In this paper review results last five increasingly intensive actin, because one hand, field has expanded with several new directions during time, other enrichment our picture will certainly provide a solid foundation impetus its future investigation.

Language: Английский

Citations

0
Bioinformatics Analysis of Actin Interactome: Characterization of the Nuclear and Cytoplasmic Actin-Binding Proteins DOI

Yakov I. Mokin,

Olga I. Povarova, Iuliia A. Antifeeva

et al.

The Protein Journal, Journal Year: 2024, Volume and Issue: 43(4), P. 675 - 682

Published: June 2, 2024

Language: Английский

Citations

2
Biological Liquid–Liquid Phase Separation, Biomolecular Condensates, and Membraneless Organelles: Now You See Me, Now You Don’t DOI Open Access
Vladimir N. Uversky

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13150 - 13150

Published: Aug. 24, 2023

Liquid–liquid phase separation (LLPS, also known as biomolecular condensation) and the related biogenesis of various membraneless organelles (MLOs) condensates (BMCs) are now considered fundamental molecular mechanisms governing spatiotemporal organization intracellular space [...]

Language: Английский

Citations

6
Kinetic trapping organizes actin filaments within liquid-like protein droplets DOI Open Access
Aravind Chandrasekaran, Kristin Graham, Jeanne C. Stachowiak

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 28, 2023

Abstract Actin is essential for various cellular functions such as growth, migration, and endocytosis. Recent evidence suggests that several actin-binding proteins phase separate to form condensates actin networks have different architectures in these droplets. In this study, we use computational modeling investigate the conditions under which forms network organizations VASP Our simulations reveal binding unbinding rates of determine probability formation shells rings, with being more probable than rings. The are highly dependent on kinetics VASP-actin interactions, suggesting they arise from kinetic trapping. Specifically, showed reducing residence time filaments promotes assembly rather where rings require a greater degree bundling. These predictions were tested experimentally using mutant VASP, has decreased bundling capability. Experiments an increase abundance droplets, consistent our predictions. Finally, investigated arrangements within deformed droplets found filament length largely determines whether droplet will straighten into bundle or remain kinetically trapped ring-like architecture. sphere-to-ellipsoid transition favored wide range while ellipse-to-rod only permitted when specific lengths. findings implications understanding how interactions between phase-separated can give rise architectures.

Language: Английский

Citations

2