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  Molecular motion and tridimensional nanoscale localization of kindlin control integrin activation in focal adhesions

Orre, T., Joly, A., Karatas, Z., Kastberger, B., Cabriel, C., Böttcher, R. T., et al. (2021). Molecular motion and tridimensional nanoscale localization of kindlin control integrin activation in focal adhesions. Nature Communications, 12(1): 3104. doi:10.1038/s41467-021-23372-w.

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 Creators:
Orre, Thomas1, Author
Joly, Adrien1, Author
Karatas, Zeynep1, Author
Kastberger, Birgit1, Author
Cabriel, Clement1, Author
Böttcher, Ralph T.2, Author              
Leveque-Fort, Sandrine1, Author
Sibarita, Jean-Baptiste1, Author
Fässler, Reinhard2, Author              
Wehrle-Haller, Bernhard1, Author
Rossier, Olivier1, Author
Giannone, Gregory1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: MEMBRANE-PROTEINS; PH DOMAIN; BINDING; TALIN; DETERMINES; REVEALS; ARCHITECTURE; FIBRONECTIN; MECHANISM; TRACKINGScience & Technology - Other Topics;
 Abstract: Focal adhesions (FAs) initiate chemical and mechanical signals involved in cell polarity, migration, proliferation and differentiation. Super-resolution microscopy revealed that FAs are organized at the nanoscale into functional layers from the lower plasma membrane to the upper actin cytoskeleton. Yet, how FAs proteins are guided into specific nano-layers to promote interaction with given targets is unknown. Using single protein tracking, super-resolution microscopy and functional assays, we link the molecular behavior and 3D nanoscale localization of kindlin with its function in integrin activation inside FAs. We show that immobilization of integrins in FAs depends on interaction with kindlin. Unlike talin, kindlin displays free diffusion along the plasma membrane outside and inside FAs. We demonstrate that the kindlin Pleckstrin Homology domain promotes membrane diffusion and localization to the membrane-proximal integrin nano-layer, necessary for kindlin enrichment and function in FAs. Using kindlin-deficient cells, we show that kindlin membrane localization and diffusion are crucial for integrin activation, cell spreading and FAs formation. Thus, kindlin uses a different route than talin to reach and activate integrins, providing a possible molecular basis for their complementarity during integrin activation. Focal adhesions (FAs) initiate chemical and mechanical signals involved in cell polarity, migration, proliferation and differentiation. Here, authors combine single protein tracking, super-resolution microscopy and functional assays, which allow correlating the molecular behaviour and 3D nanoscale localization of kindlin with its function in integrin activation inside FAs.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published online
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 12 (1) Sequence Number: 3104 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723