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

Autor: Birgit Kastberger, Adrien Joly, Ralph T. Böttcher, Reinhard Fässler, Zeynep Karatas, Bernhard Wehrle-Haller, Thomas Orré, Jean-Baptiste Sibarita, Clément Cabriel, Olivier Rossier, Sandrine Lévêque-Fort, Grégory Giannone
Přispěvatelé: Interdisciplinary Institute for Neuroscience (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Integrins
[SDV]Life Sciences [q-bio]
General Physics and Astronomy
Muscle Proteins
Plasma protein binding
Mice
0302 clinical medicine
Cells
Cultured
Mice
Knockout
[PHYS]Physics [physics]
Cultured
Multidisciplinary
biology
Chemistry
Membrane Proteins/genetics/metabolism
Cell biology
Neoplasm Proteins
Pleckstrin homology domain
Cytoskeletal Proteins/genetics/metabolism
Protein Binding
Muscle Proteins/genetics/metabolism
Cells
Knockout
Science
Integrin
Biophysics
Neoplasm Proteins/genetics/metabolism
General Biochemistry
Genetics and Molecular Biology
Article
Focal adhesion
03 medical and health sciences
Motion
Cell Adhesion
Animals
Humans
ddc:612
Cell adhesion
Focal Adhesions
Binding Sites
Cell Membrane/metabolism
Focal Adhesions/metabolism
Cell Membrane
Membrane Proteins
General Chemistry
Actin cytoskeleton
Fibronectin
Cytoskeletal Proteins
030104 developmental biology
Membrane protein
Mutation
Integrins/genetics/metabolism
biology.protein
030217 neurology & neurosurgery
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021)
Nature Communications
Nature Communications, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-021-23372-w⟩
Nature Communications, Vol. 12, No 1 (2021) P. 3104
ISSN: 2041-1723
Popis: 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.
Databáze: OpenAIRE
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