Focal adhesions contain three specialized actin nanoscale layers

Focal adhesions (FAs) connect inner workings of cell to the extracellular matrix to control cell adhesion, migration and mechanosensing. Previous studies demonstrated that FAs contain three vertical layers, which connect extracellular matrix to the cytoskeleton. By using super-resolution iPALM micro...

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Published inNature communications Vol. 15; no. 1; p. 2547
Main Authors Kumari, Reena, Ven, Katharina, Chastney, Megan, Kokate, Shrikant B, Peränen, Johan, Aaron, Jesse, Kogan, Konstantin, Almeida-Souza, Leonardo, Kremneva, Elena, Poincloux, Renaud, Chew, Teng-Leong, Gunning, Peter W, Ivaska, Johanna, Lappalainen, Pekka
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 21.03.2024
Nature Portfolio
Subjects
Actin
Actin Cytoskeleton - metabolism
Actinin
Actins - metabolism
Adhesion
Cell adhesion
Cell migration
Cytoskeleton
Cytoskeleton - metabolism
Dismantling
Extracellular matrix
Filaments
Focal Adhesions - metabolism
Isoforms
Life Sciences
Protein Isoforms - metabolism
Tropomyosin
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Summary:Focal adhesions (FAs) connect inner workings of cell to the extracellular matrix to control cell adhesion, migration and mechanosensing. Previous studies demonstrated that FAs contain three vertical layers, which connect extracellular matrix to the cytoskeleton. By using super-resolution iPALM microscopy, we identify two additional nanoscale layers within FAs, specified by actin filaments bound to tropomyosin isoforms Tpm1.6 and Tpm3.2. The Tpm1.6-actin filaments, beneath the previously identified α-actinin cross-linked actin filaments, appear critical for adhesion maturation and controlled cell motility, whereas the adjacent Tpm3.2-actin filament layer beneath seems to facilitate adhesion disassembly. Mechanistically, Tpm3.2 stabilizes ACF-7/MACF1 and KANK-family proteins at adhesions, and hence targets microtubule plus-ends to FAs to catalyse their disassembly. Tpm3.2 depletion leads to disorganized microtubule network, abnormally stable FAs, and defects in tail retraction during migration. Thus, FAs are composed of distinct actin filament layers, and each may have specific roles in coupling adhesions to the cytoskeleton, or in controlling adhesion dynamics.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-46868-7