ArticleProceedings of the National Academy of Sciences of the United States of America2013
Integrin-dependent force transmission to the extracellular matrix by α-actinin triggers adhesion maturation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
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Who cites it
165 citing papers in PubMed, 280 citations in OpenAlex.
- Protein force spectroscopy using magnetic tweezers: Slow and steady wins the race?Biophysical journal · 2026Review
- Mechanisms of actin-binding proteins in glycolysis-cytoskeleton coupling.Journal of translational medicine · 2026Review
- Magnetic torque-mediated early asymmetric mechanical stimulation directs structural and functional maturation in human cardiac organoids.Scientific reports · 2026Article
- Reconstituted nascent adhesion condensates drive actin polymerization on supported lipid bilayers.Science advances · 2026Article
- AAK1-mediated phosphorylation of PDLIM5 and Talin1 promotes focal adhesion disassembly to accelerate cell migration.Nature communications · 2026Article
- Timing Mechanotransduction: Mechanically Dynamic Biomaterials Reveal the Temporal Hierarchy of YAP/TAZ Control Nodes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Zona pellucida is required for oocyte actin cortex and oocyte-somatic cell interactions during oocyte growth.Cell death discovery · 2026Article
- Cell shape and maturation impacts α-actinin-2 tension in iPSC-derived cardiomyocytes.APL bioengineering · 2026Article
- GABA-independent activation of GABANature communications · 2025Article
- Alpha-actinin-1 promotes adhesion maturation and facilitates sarcomere assembly in cardiac myocytes.Molecular biology of the cell · 2025Article
- α-Actinin-1 in Megakaryocytes: Its Structure, Interacting Proteins and Implications for Thrombopoiesis.Biomedicines · 2025Review
- The bidirectional interplay between RNA processing and mechanotransduction.Cell reports · 2025Review
- miRNA-29 regulates epidermal and mesenchymal functions in skin repair.FEBS letters · 2025Article
- Mechanotransduction and Skeletal Muscle Atrophy: The Interplay Between Focal Adhesions and Oxidative Stress.International journal of molecular sciences · 2025Review
- Nanoscale distribution of bioactive ligands on biomaterials regulates cell mechanosensing through translocation of actin into the nucleus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural and functional insights into α-actinin isoforms and their implications in cardiovascular disease.The Journal of general physiology · 2025Review
- G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration.Cell reports · 2025Article
- The role and regulation of integrins in cell migration and invasion.Nature reviews. Molecular cell biology · 2025Review
- Integrin and Its Associated Proteins as a Mediator for Mechano-Signal Transduction.Biomolecules · 2025Review
- Physical principles and mechanisms of cell migration.npj biological physics and mechanics · 2025Review
105 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Focal adhesions are mechanosensitive elements that enable mechanical communication between cells and the extracellular matrix. Here, we demonstrate a major mechanosensitive pathway in which α-actinin triggers adhesion maturation by linking integrins to actin in nascent adhesions. We show that depletion of the focal adhesion protein α-actinin enhances force generation in initial adhesions on fibronectin, but impairs mechanotransduction in a subsequent step, preventing adhesion maturation. Expression of an α-actinin fragment containing the integrin binding domain, however, dramatically reduces force generation in depleted cells. This behavior can be explained by a competition between talin (which mediates initial adhesion and force generation) and α-actinin for integrin binding. Indeed, we show in an in vitro assay that talin and α-actinin compete for binding to β3 integrins, but cooperate in binding to β1 integrins. Consistently, we find opposite effects of α-actinin depletion and expression of mutants on substrates that bind β3 integrins (fibronectin and vitronectin) versus substrates that only bind β1 integrins (collagen). We thus suggest that nascent adhesions composed of β3 integrins are initially linked to the actin cytoskeleton by talin, and then α-actinin competes with talin to bind β3 integrins. Force transmitted through α-actinin then triggers adhesion maturation. Once adhesions have matured, α-actinin recruitment correlates with force generation, suggesting that α-actinin is the main link transmitting force between integrins and the cytoskeleton in mature adhesions. Such a multistep process enables cells to adjust forces on matrices, unveiling a role of α-actinin that is different from its well-studied function as an actin cross-linker.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.