Inhibition of Arp2/3 Complex after ADP-Ribosylation of Arp2 by Binary <i>Clostridioides</i> Toxins
Clostridioides bacteria are responsible for life threatening infections. Here, we show that in addition to actin, the binary toxins CDT, C2I, and Iota from <i>Clostridioides difficile</i>, <i>botulinum</i>, and <i>perfrigens</i>, respectively, ADP-ribosylate the a...
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| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/22/3661 |
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| author | Carsten Schwan Alexander E. Lang Andreas Schlosser Setsuko Fujita-Becker Abdulatif AlHaj Rasmus R. Schröder Jan Faix Klaus Aktories Hans Georg Mannherz |
| author_facet | Carsten Schwan Alexander E. Lang Andreas Schlosser Setsuko Fujita-Becker Abdulatif AlHaj Rasmus R. Schröder Jan Faix Klaus Aktories Hans Georg Mannherz |
| author_sort | Carsten Schwan |
| collection | DOAJ |
| description | Clostridioides bacteria are responsible for life threatening infections. Here, we show that in addition to actin, the binary toxins CDT, C2I, and Iota from <i>Clostridioides difficile</i>, <i>botulinum</i>, and <i>perfrigens</i>, 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. |
| first_indexed | 2024-03-09T18:25:28Z |
| format | Article |
| id | doaj.art-7d6ce74fc3d84675acfc919b8dc00849 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T18:25:28Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-7d6ce74fc3d84675acfc919b8dc008492023-11-24T07:59:00ZengMDPI AGCells2073-44092022-11-011122366110.3390/cells11223661Inhibition of Arp2/3 Complex after ADP-Ribosylation of Arp2 by Binary <i>Clostridioides</i> ToxinsCarsten Schwan0Alexander E. Lang1Andreas Schlosser2Setsuko Fujita-Becker3Abdulatif AlHaj4Rasmus R. Schröder5Jan Faix6Klaus Aktories7Hans Georg Mannherz8Institute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, Albert-Ludwig-University, 79104 Freiburg, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, Albert-Ludwig-University, 79104 Freiburg, GermanyRudolf Virchow Center of Experimental Biomedicine, University of Würzburg, 97080 Würzburg, GermanyCryo-Electron Microscopy, BioQuant, University Hospital, 69120 Heidelberg, GermanyDepartment of Anatomy and Molecular Embryology, Ruhr-University, 44780 Bochum, GermanyCryo-Electron Microscopy, BioQuant, University Hospital, 69120 Heidelberg, GermanyInstitute of Biophysical Chemistry, Hannover Medical School, 30625 Hannover, GermanyInstitute of Experimental and Clinical Pharmacology and Toxicology, Faculty of Medicine, Albert-Ludwig-University, 79104 Freiburg, GermanyDepartment of Anatomy and Molecular Embryology, Ruhr-University, 44780 Bochum, GermanyClostridioides bacteria are responsible for life threatening infections. Here, we show that in addition to actin, the binary toxins CDT, C2I, and Iota from <i>Clostridioides difficile</i>, <i>botulinum</i>, and <i>perfrigens</i>, 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.https://www.mdpi.com/2073-4409/11/22/3661actinADP-ribosyltransferasesArp2/3 complex<i>Clostridioides</i> binary toxins |
| spellingShingle | Carsten Schwan Alexander E. Lang Andreas Schlosser Setsuko Fujita-Becker Abdulatif AlHaj Rasmus R. Schröder Jan Faix Klaus Aktories Hans Georg Mannherz Inhibition of Arp2/3 Complex after ADP-Ribosylation of Arp2 by Binary <i>Clostridioides</i> Toxins Cells actin ADP-ribosyltransferases Arp2/3 complex <i>Clostridioides</i> binary toxins |
| title | Inhibition of Arp2/3 Complex after ADP-Ribosylation of Arp2 by Binary <i>Clostridioides</i> Toxins |
| title_full | Inhibition of Arp2/3 Complex after ADP-Ribosylation of Arp2 by Binary <i>Clostridioides</i> Toxins |
| title_fullStr | Inhibition of Arp2/3 Complex after ADP-Ribosylation of Arp2 by Binary <i>Clostridioides</i> Toxins |
| title_full_unstemmed | Inhibition of Arp2/3 Complex after ADP-Ribosylation of Arp2 by Binary <i>Clostridioides</i> Toxins |
| title_short | Inhibition of Arp2/3 Complex after ADP-Ribosylation of Arp2 by Binary <i>Clostridioides</i> Toxins |
| title_sort | inhibition of arp2 3 complex after adp ribosylation of arp2 by binary i clostridioides i toxins |
| topic | actin ADP-ribosyltransferases Arp2/3 complex <i>Clostridioides</i> binary toxins |
| url | https://www.mdpi.com/2073-4409/11/22/3661 |
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