Inhibition of Arp2/3 complex after ADP-ribosylation of Arp2 by binary Clostridioides toxins

Please always quote using this URN: urn:nbn:de:bvb:20-opus-297454
  • Clostridioides bacteria are responsible for life threatening infections. Here, we show that in addition to actin, the binary toxins CDT, C2I, and Iota from Clostridioides difficile, botulinum, and perfrigens, respectively, ADP-ribosylate the actin-related protein Arp2 of Arp2/3 complex and its additional components ArpC1, ArpC2, and ArpC4/5. The Arp2/3 complex is composed of seven subunits and stimulates the formation of branched actin filament networks. This activity is inhibited after ADP-ribosylation of Arp2. Translocation of theClostridioides bacteria are responsible for life threatening infections. Here, we show that in addition to actin, the binary toxins CDT, C2I, and Iota from Clostridioides difficile, botulinum, and perfrigens, respectively, ADP-ribosylate the actin-related protein Arp2 of Arp2/3 complex and its additional components ArpC1, ArpC2, and ArpC4/5. The Arp2/3 complex is composed of seven subunits and stimulates the formation of branched actin filament networks. This activity is inhibited after ADP-ribosylation of Arp2. Translocation of the ADP-ribosyltransferase component of CDT toxin into human colon carcinoma Caco2 cells led to ADP-ribosylation of cellular Arp2 and actin followed by a collapse of the lamellipodial extensions and F-actin network. Exposure of isolated mouse colon pieces to CDT toxin induced the dissolution of the enterocytes leading to luminal aggregation of cellular debris and the collapse of the mucosal organization. Thus, we identify the Arp2/3 complex as hitherto unknown target of clostridial ADP-ribosyltransferases.show moreshow less

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Metadaten
Author: Carsten Schwan, Alexander E. Lang, Andreas Schlosser, Setsuko Fujita-Becker, Abdulatif AlHaj, Rasmus R. Schröder, Jan Faix, Klaus Aktories, Hans Georg Mannherz
URN:urn:nbn:de:bvb:20-opus-297454
Document Type:Journal article
Faculties:Fakultät für Biologie / Rudolf-Virchow-Zentrum
Language:English
Parent Title (English):Cells
ISSN:2073-4409
Year of Completion:2022
Volume:11
Issue:22
Article Number:3661
Source:Cells (2022) 11:22, 3661. https://doi.org/10.3390/cells11223661
DOI:https://doi.org/10.3390/cells11223661
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:ADP-ribosyltransferases; Arp2/3 complex; Clostridioides binary toxins; actin
Release Date:2023/10/16
Date of first Publication:2022/11/18
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International