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Shigella IpaA mediates actin bundling through diffusible vinculin oligomers with activation imprint

Valencia-Gallardo, Cesar ; Aguilar-Salvador, Daniel Isui ; Khakzad, Hamed ; Cocom-Chan, Benjamin ; Bou-Nader, Charles ; Velours, Christophe ; Zarrouk, Yosra ; Le Clainche, Christophe ; Malosse, Christian and Lima, Diogo Borges , et al. (2023) In Cell Reports 42(4).
Abstract

Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domains that bind to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain, leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing... (More)

Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domains that bind to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain, leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing drugs. Unlike canonical activation, vinculin homo-oligomers induced by IpaA appear to keep a persistent imprint of the activated state in addition to their bundling activity, accounting for stable cell adhesion independent of force transduction and relevant to bacterial invasion.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
actin, adhesion, bundling, CP: Cell biology, CP: Microbiology, invasion, Shigella, vinculin
in
Cell Reports
volume
42
issue
4
article number
112405
publisher
Cell Press
external identifiers
  • pmid:37071535
  • scopus:85152539214
ISSN
2211-1247
DOI
10.1016/j.celrep.2023.112405
language
English
LU publication?
yes
id
8dd19aec-f2d1-4dc7-a1f7-5de558dbfaf1
date added to LUP
2023-10-09 12:40:26
date last changed
2024-04-19 02:07:28
@article{8dd19aec-f2d1-4dc7-a1f7-5de558dbfaf1,
  abstract     = {{<p>Upon activation, vinculin reinforces cytoskeletal anchorage during cell adhesion. Activating ligands classically disrupt intramolecular interactions between the vinculin head and tail domains that bind to actin filaments. Here, we show that Shigella IpaA triggers major allosteric changes in the head domain, leading to vinculin homo-oligomerization. Through the cooperative binding of its three vinculin-binding sites (VBSs), IpaA induces a striking reorientation of the D1 and D2 head subdomains associated with vinculin oligomerization. IpaA thus acts as a catalyst producing vinculin clusters that bundle actin at a distance from the activation site and trigger the formation of highly stable adhesions resisting the action of actin relaxing drugs. Unlike canonical activation, vinculin homo-oligomers induced by IpaA appear to keep a persistent imprint of the activated state in addition to their bundling activity, accounting for stable cell adhesion independent of force transduction and relevant to bacterial invasion.</p>}},
  author       = {{Valencia-Gallardo, Cesar and Aguilar-Salvador, Daniel Isui and Khakzad, Hamed and Cocom-Chan, Benjamin and Bou-Nader, Charles and Velours, Christophe and Zarrouk, Yosra and Le Clainche, Christophe and Malosse, Christian and Lima, Diogo Borges and Quenech'Du, Nicole and Mazhar, Bilal and Essid, Sami and Fontecave, Marc and Asnacios, Atef and Chamot-Rooke, Julia and Malmström, Lars and Tran Van Nhieu, Guy}},
  issn         = {{2211-1247}},
  keywords     = {{actin; adhesion; bundling; CP: Cell biology; CP: Microbiology; invasion; Shigella; vinculin}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  publisher    = {{Cell Press}},
  series       = {{Cell Reports}},
  title        = {{Shigella IpaA mediates actin bundling through diffusible vinculin oligomers with activation imprint}},
  url          = {{http://dx.doi.org/10.1016/j.celrep.2023.112405}},
  doi          = {{10.1016/j.celrep.2023.112405}},
  volume       = {{42}},
  year         = {{2023}},
}