Article
Multidisciplinary Sciences
Ernest Iu, Alexander Bogatch, Sergey Plotnikov
Summary: Cell spreading is a dynamic process where a cell attaches to a substrate and forms thin lamellipodia, crucial for cell morphology and mechanical forces. Cell spreading assays are used to assess lamellipodial dynamics, but a detailed experimental workflow and data analysis tools are currently lacking.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Biology
F. Leyden, S. Uthishtran, U. K. Moorthi, H. M. York, A. Patil, H. Gandhi, E. P. Petrov, T. Bornschlogl, S. Arumugam
Summary: Combining LLSM and optogenetics allows for precise control over the generation of membrane protrusions, demonstrating that continuous activation of Rac1 leads to sustained actin polymerization and ruffling. This approach can be used to study complex morpho-dynamics and protein enrichment in the protrusions, showing that Rac1 activation can generate untemplated, lamellar protrusions.
Article
Cell Biology
Xuemeng Shi, Zeyu Wen, Yajun Wang, Yan-Jun Liu, Kun Shi, Yaming Jiu
Summary: This study reveals a negative feedback regulation between actin and CAV-1 that influences directional cell migration. Inhibition of contractile stress fibers leads to decreased phosphorylation of CAV-1, affecting the size and motility of cytoplasmic CAV-1 vesicles. Defects in CAV-1 result in disordered cell structures and compromised cell migration directionality.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Atsuko Niimi, Siripan Limsirichaikul, Keiko Kano, Yasuyoshi Mizutani, Toshiyuki Takeuchi, Patinya Sawangsri, Dat Quoc Tran, Yoshiyuki Kawamoto, Motoshi Suzuki
Summary: In this study, CERS6 binding partners were identified using co-immunoprecipitation, liquid chromatography, and tandem mass spectrometry analysis. Among the candidates, LASP1 was found to play a role in cell migration and interact with actin on lamellipodia along with CERS6. Silencing of CERS6 and/or LASP1 resulted in reduced levels of lamellipodia formation and cell migration. The interaction of CERS6 or LASP1 with actin was also decreased when the partner was depleted. Based on these findings, it is proposed that LASP1-CERS6 interaction promotes cancer cell migration.
Article
Cell Biology
Vassilis Papalazarou, Laura M. Machesky
Summary: The Arp2/3 complex coordinates the formation of branched actin networks, which are sensitive to mechanical forces and allow cells to generate pushing forces, influencing cellular processes.
CURRENT OPINION IN CELL BIOLOGY
(2021)
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
Multidisciplinary Sciences
Cristiane J. Nunes-Santos, HyeSun Kuehn, Brigette Boast, SuJin Hwang, Douglas B. Kuhns, Jennifer Stoddard, Julie E. Niemela, Danielle L. Fink, Stefania Pittaluga, Mones Abu-Asab, John S. Davies, Valarie A. Barr, Tomoki Kawai, Ottavia M. Delmonte, Marita Bosticardo, Mary Garofalo, Magda Carneiro-Sampaio, Raz Somech, Mohammad Gharagozlou, Nima Parvaneh, Lawrence E. Samelson, Thomas A. Fleisher, Anne Puel, Luigi D. Notarangelo, Bertrand Boisson, Jean-Laurent Casanova, Beata Derfalvi, Sergio D. Rosenzweig
Summary: This study describes the first cases of germline biallelic null mutations in ARPC5, a subunit of the Arp2/3 actin nucleator complex. These mutations disrupt actin function and cytokine signaling, causing a range of symptoms including infections, autoimmunity, inflammation, and dysmorphisms. Additionally, the study demonstrates the distinctive impact of this syndrome on interleukin-6 (IL-6) signaling.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Gleb Simanov, Irene Dang, Artem I. Fokin, Ksenia Oguievetskaia, Valerie Campanacci, Jacqueline Cherfils, Alexis M. Gautreau
Summary: In the process of cell migration, Arpin interacts with Tankyrase 1 and 2 (TNKS) and Arp2/3 to regulate migration persistence through two independent pathways. The mutation affecting interactions with both TNKS and Arp2/3 renders Arpin completely inactive, suggesting the importance of these interactions in controlling migration persistence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Yanan Wang, Giovanni Chiappetta, Raphael Guerois, Yijun Liu, Stephane Romero, Daniel J. Boesch, Matthias Krause, Claire A. Dessalles, Avin Babataheri, Abdul I. Barakat, Baoyu Chen, Joelle Vinh, Anna Polesskaya, Alexis M. Gautreau
Summary: The RAC1-WAVE-Arp2/3 signaling pathway generates branched actin networks that power lamellipodium protrusion of migrating cells. PPP2R1A is a protein that associates with the WAVE complex subunit ABI1 when RAC1 is activated and branched actin generation is blocked. PPP2R1A interacts with the WAVE Shell Complex at the lamellipodial edge and is required for migration persistence and RAC1-dependent actin polymerization. Mutations in PPP2R1A impair WAVE Shell Complex binding and migration regulation, suggesting its essential role in cell migration.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Shashi Prakash Singh, Peggy Paschke, Luke Tweedy, Robert H. Insall
Summary: PKB and SGK kinases play crucial roles in pseudopodia formation and cell motility, particularly in actin polymerization and recruitment of the Arp2/3 complex by the Scar/WAVE complex.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
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
Agriculture, Dairy & Animal Science
Meng-Hao Pan, Rui Xu, Yiqian Zhang, Lu Yin, Ruoyu Li, Dongxu Wen, Sihai Lu, Yan Gao, Xiaoe Zhao, Qiang Wei, Bin Han, Baohua Ma
Summary: Our study demonstrates that the Arp2/3 complex is essential for maintaining cytoskeletal dynamics and mitochondrial function during goat oocyte maturation. Disruption of the Arp2/3 complex leads to impaired F-actin assembly, spindle organization, ROS accumulation, and increased early apoptosis in goat oocytes.
Article
Multidisciplinary Sciences
Fred E. Fregoso, Malgorzata Boczkowska, Grzegorz Rebowski, Peter J. Carman, Trevor van Eeuwen, Roberto Dominguez
Summary: Cortactin coactivates with NPFs to stabilize branched networks by linking Arp2/3 complex to F-actin. Cortactin's Acidic domain binds Arp2/3 complex through a reversal binding site and its N- and C-terminal sequences contribute to coactivation with NPFs.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Steven Z. Chou, Moon Chatterjee, Thomas D. Pollard
Summary: By analyzing the images collected by electron cryo-microscopy, we reconstructed the structure of actin filament branch junctions formed by fission yeast Arp2/3 complex. The formation of this structure requires a conformational change of the Arp2/3 complex and the acquisition of a new buried surface area to maintain the stability of the branch.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Emiliano Molina, Vicente F. Cataldo, Cristian Eggers, Valentina Munoz-Madrid, Alvaro Glavic
Summary: Cells use membrane protrusions like lamellipodia and filopodia to sense, move, and form new contacts. The Arp2/3 complex and actomyosin contractile system play important roles in these processes. This study investigated the role of Prpk, a protein kinase, in cell shape changes and found that reductions in Prpk alter cell shape and lamellipodia structure. Prpk interacts with proteins involved in actin filament dynamics and is essential for proper Arp2/3 complex distribution and actin dynamics during immune response.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Tadamoto Isogai, Metello Innocenti
BIOCHEMICAL SOCIETY TRANSACTIONS
(2016)
Article
Biochemistry & Molecular Biology
Katarzyna M. Kedziora, Tadamoto Isogai, Kees Jalink, Metello Innocenti
FRONTIERS IN BIOSCIENCE-LANDMARK
(2016)
Article
Biology
Daniela Leyton-Puig, Katarzyna M. Kedziora, Tadamoto Isogai, Bram van den Broek, Kees Jalink, Metello Innocenti
Meeting Abstract
Oncology
Hilda De Vries, Ji-Ying Song, Tadamoto Isogai, Metello Innocenti, Iris De Rink, Rajith Bhaskaran, Oscar Krijgsman, Anton Berns
JOURNAL OF THORACIC ONCOLOGY
(2017)
Article
Multidisciplinary Sciences
Daniela Leyton-Puig, Tadamoto Isogai, Elisabetta Argenzio, Bram van den Broek, Jeffrey Klarenbeek, Hans Janssen, Kees Jalink, Metello Innocenti
NATURE COMMUNICATIONS
(2017)
Article
Biochemistry & Molecular Biology
Elisabetta Argenzio, Jeffrey Klarenbeek, Katarzyna M. Kedziora, Leila Nahidiazar, Tadamoto Isogai, Anastassis Perrakis, Kees Jalink, Wouter H. Moolenaar, Metello Innocenti
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Elisabetta Argenzio, Metello Innocenti
Article
Medicine, Research & Experimental
Michael Cangkrama, Mateusz Wietecha, Nicolas Mathis, Rin Okumura, Luca Ferrarese, Dunja Al-Nuaimi, Maria Antsiferova, Reinhard Dummer, Metello Innocenti, Sabine Werner
EMBO MOLECULAR MEDICINE
(2020)
Article
Gastroenterology & Hepatology
Yamin Zhao, Benjamin Schoeps, Dianbo Yao, Zhiheng Zhang, Kathleen Schuck, Vivien Tissen, Carsten Jaeger, Anna Melissa Schlitter, Rob van der Kammen, Christina Ludwig, Jan G. D'Haese, Susanne Raulefs, Nadja Maeritz, Shanshan Shen, Xiaoping Zou, Achim Krueger, Jorg Kleeff, Christoph W. Michalski, Helmut Friess, Metello Innocenti, Bo Kong
Summary: mTORC1 and mTORC2 play a dual, nonredundant regulatory role in ADM and early pancreatic carcinogenesis by promoting the function of the Arp2/3 complex. The Arp2/3 complex acts as a common effector of mTORC1 and mTORC2, connecting oncogenic signals with actin dynamics in PDAC initiation.
Article
Microbiology
Aaron S. Dhanda, A. Wayne Vogl, Fern Ness, Metello Innocenti, Julian A. Guttman
Summary: Direct cell-to-cell spreading of Listeria monocytogenes requires the induction of actin-based membrane protrusions in donor cells, which are endocytosed by adjacent receiving cells. Formin mDia1 plays a vital role in the assembly of the F-actin shell during this process, leading to efficient cell-to-cell transfer of the bacteria.
Article
Oncology
Michael Cangkrama, Huan Liu, James Whipman, Maria Zubair, Mai Matsushita, Michela Di Filippo, Manfred Kopf, Metello Innocenti, Sabine Werner
Summary: This study reveals the crucial role of mitochondria in the protumorigenic CAF phenotype and identifies the activin A-mDia2-MIRO1 signaling axis as a potential diagnostic and therapeutic target in CAFs.
Review
Biochemistry & Molecular Biology
Metello Innocenti
Summary: The mammalian formin family includes fifteen multi-domain proteins that regulate actin dynamics and microtubules. The small molecule inhibitor of formin homology 2 domains (SMIFH2) has provided a powerful tool to study formins. However, there are still controversies and open questions regarding the substrates and mechanism of action of SMIFH2, but it remains useful in studying formins in health and disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Martina Del Nero, Alessandro Colombo, Stefania Garbujo, Chiara Baioni, Linda Barbieri, Metello Innocenti, Davide Prosperi, Miriam Colombo, Luisa Fiandra
Summary: The interaction between tumor cells and activated fibroblasts plays a critical role in the malignant features of desmoplastic carcinomas. Transforming growth factor beta (TGF-beta) and Platelet-Derived Growth Factor (PDGF) contribute to the pro-tumorigenic phenotypes in fibroblasts, while Interleukin-6 (IL-6) released by activated fibroblasts enhances tumor-cell invasiveness and chemoresistance. This study validates the use of advanced cell culture models to investigate the interplay between mammary tumor cells and fibroblasts, revealing the role of TGF-beta, PDGF, and IL-6 in breast cancer progression.
Article
Developmental Biology
Rob van der Kammen, Ji-Ying Song, Iris de Rink, Hans Janssen, Stefania Madonna, Claudia Scarponi, Cristina Albanesi, Wim Brugman, Metello Innocenti