Article
Multidisciplinary Sciences
Bojian Ding, Heidy Y. Narvaez-Ortiz, Yuvraj Singh, Glen M. Hocky, Saikat Chowdhury, Brad J. Nolen
Summary: Arp2/3 complex nucleates branched actin filaments and provides pushing forces for cellular processes. This study reveals the contacts between Arp2/3 complex and the mother actin filament, suggesting that actin filaments stimulate subunit flattening for complex activation. However, limited contact between the bottom half of the complex and the mother filament may explain why actin filaments are required but insufficient to trigger nucleation during WASP-mediated activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Luyan Cao, Foad Ghasemi, Michael Way, Antoine Jegou, Guillaume Romet-Lemonne
Summary: Activation of the Arp2/3 complex by actin nucleation-promoting factors leads to the formation of branching actin filaments, while direct nucleation of linear actin filaments is induced by SPIN90-Arp2/3. Interestingly, the VCA motifs of certain proteins destabilize existing branches and linear filament ends. However, branch stabilizer cortactin and destabilizer GMF have similar effects on SPIN90-activated Arp2/3. These findings highlight the importance of understanding the similarities and differences between the two mechanisms in regulating actin cytoskeleton dynamics, as well as the differential responses of branched and linear filaments to aging and mechanical stress.
Article
Cell Biology
Shuting Zhang, Dimitrios Vavylonis
Summary: The nucleation of actin filament branches by the Arp2/3 complex involves activation through nucleation promotion factors (NPFs), recruitment of actin monomers, and binding of the complex to the side of actin filaments. Our molecular dynamics simulations using a coarse-grained model revealed stable configurations of the Arp2/3 complex with actin monomers and the activating VCA domain of the NPF Wiskott-Aldrich syndrome protein, supporting prior structural studies and providing insight into mechanisms proposed in previous studies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
William J. Spencer, Nicholas F. Schneider, Tylor R. Lewis, Carson M. Castillo, Nikolai P. Skiba, Vadim Y. Arshavsky
Summary: The photoreceptor outer segment is a cilium filled with flat-tened disc membranes for light capture. The addition of new discs at the base of outer segments is driven by Arp2/3-mediated actin polymerization initiated by the pentameric WAVE complex. Knockout of WASF3, a subunit of the WAVE complex, disrupts actin polymerization and leads to disorganized membrane lamellae instead of a proper outer segment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Malou Zuidscherwoude, Elizabeth J. Haining, Victoria A. Simms, Stephanie Watson, Beata Grygielska, Alex T. Hardy, Andrea Bacon, Stephen P. Watson, Steven G. Thomas
Summary: The formin family plays a critical role in cytoskeletal dynamics and platelet formation, with a specific importance in megakaryocyte function. Knockout mice lacking two formin proteins exhibit macrothrombocytopenia due to aberrant megakaryocyte function and a slight decrease in platelet lifespan, while platelet function remains unaffected.
Article
Biochemistry & Molecular Biology
Zhiming Ma, Kexin Zhu, Yong-Gui Gao, Suet-Mien Tan, Yansong Miao
Summary: The actin cytoskeleton undergoes rapid remodelling during signal transduction, and the plant class I formin family plays a major role in this process. The PM-integrated formins are highly responsive to mechanical perturbation, regulating their condensation on the cell surface. However, the molecular mechanisms underlying the mechanosensing and mechanoregulation of formin in actin remodelling remain unclear.
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
Pharmacology & Pharmacy
Artem I. Fokin, Roman N. Chuprov-Netochin, Alexander S. Malyshev, Stephane Romero, Marina N. Semenova, Leonid D. Konyushkin, Sergey V. Leonov, Victor V. Semenov, Alexis M. Gautreau
Summary: Several compounds structurally related to CK-666 were found to suppress Arp2/3 activation, and two of them demonstrated improved in vivo efficiency compared to CK-666.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Cell Biology
Emmanuel Martin, Magali Suzanne
Summary: This review discusses the role of the actin nucleation complex Arp2/3 in epithelial tissue, including its influence on cell-cell cooperation and tissue morphogenesis. It plays a significant role in regulating cell-cell adhesion, intracellular trafficking, and protrusion formation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Pengbo Liang, Clara Schmitz, Beatrice Lace, Franck Anicet Ditengou, Chao Su, Eija Schulze, Julian Knerr, Robert Grosse, Jean Keller, Cyril Libourel, Pierre-Marc Delaux, Thomas Ott
Summary: Legumes have the ability to associate with rhizobia for nitrogen-fixing root nodule symbiosis. In Medicago truncatula, root hair colonization by Sinorhizobium meliloti begins from young root hairs, which physically entwine around the symbiont to form rhizobial traps. This unique process involves alterations in membrane organization, cytosolic calcium gradient, actin rearrangements, and symbiotic responses in legumes.
Article
Pharmacology & Pharmacy
Coralie Mergault, Fanny Lisee, Victor Tiroille, Melia Magnien, Christelle Parent, Woodys Lenga Mabonda, Damien Sizaret, Madeleine Jaillet, Bruno Crestani, Sylvain Marchand-Adam, Laurent Plantier
Summary: The study found that the expression of the Arp2/3 complex was increased in profibrotic environments in vitro and in vivo. Inhibition of the Arp2/3 complex repressed ACTA2 and COL1 expression and blocked the Akt/phospho-GSK3 beta/beta-catenin/MRTF-A pathway in lung fibroblasts. CK666 demonstrated antifibrotic properties in the lung in vivo.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Marcel Hahn, Adriana Covarrubias-Pinto, Lina Herhaus, Shankha Satpathy, Kevin Klann, Keith B. Boyle, Christian Munch, Krishnaraj Rajalingam, Felix Randow, Chunaram Choudhary, Ivan Dikic
Summary: SIK2 kinase is a central component of the host defense machinery during Salmonella infection, and its depletion can lead to bacterial escape and impaired Xenophagy. During bacterial infection, SIK2 associates with actin and is recruited to the Salmonella-containing vacuole, controlling the formation of a protective SCV actin shield.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Julian Knerr, Ralf Werner, Carsten Schwan, Hong Wang, Peter Gebhardt, Helga Groetsch, Almuth Caliebe, Malte Spielmann, Paul-Martin Holterhus, Robert Grosse, Nadine C. Hornig
Summary: Steroid hormone receptors are crucial for mammalian physiology and are involved in various conditions. Functional mutations in DAAM2 gene were found in patients with androgen insensitivity syndrome. DAAM2 is enriched in the nucleus and forms actin-dependent transcriptional droplets with AR in response to dihydrotestosterone, promoting gene expression and cellular functions. Our study reveals the signal-regulated nuclear actin assembly at a steroid hormone receptor, which is necessary for transcription.
Review
Microbiology
Autumn Paluck, Jaspreet Osan, Lauren Hollingsworth, Sattya Narayan Talukdar, Ali Al Saegh, Masfique Mehedi
Summary: RSV is a major viral factor causing pneumonia in children worldwide. The virus interacts with the host actin cytoskeleton, particularly the ARP2/3 complex, to facilitate its replication and spread. Understanding the modulation of the cytoskeleton by RSV and its role in lung pathobiology may lead to novel intervention strategies.
Article
Cell Biology
Ingrid Billault-Chaumartin, Laetitia Michon, Caitlin A. Anderson, Sarah E. Yde, Cristian Suarez, Justyna Iwaszkiewicz, Vincent Zoete, David R. Kovar, Sophie G. Martin
Summary: In formin-family proteins, the nucleation and elongation activities of actin filaments are located in the formin homology 1 (FH1) and FH2 domains, with varying reaction rates among different formins. This study investigates the importance of nucleation and elongation rates of formins in vivo using the formin Fus1 in Schizosaccharomyces pombe. It is found that changes in the nucleation and elongation rates have direct effects on the architecture of the actin fusion focus, and that Fus1's native high nucleation and low elongation rates are optimal for assembly of the fusion focus. A point mutant in the FH2 domain of Fus1 is also identified, which preserves the native nucleation and elongation rates in vitro but alters the function in vivo, indicating additional properties of the FH2 domain. Thus, the rates of actin assembly are tailored for assembly of specific actin structures.
JOURNAL OF CELL SCIENCE
(2022)
