Journal of Cell ScienceJulien Pernier, Marcelina Cardoso Dos Santos, Christophe Le Clainche and colleagues dissect the role of talin and kindlin in integrin clustering, describing their synergistic effects in enhancing cell adhesion.
Highlight: https://journals.biologists.com/jcs/article/136/8/e136_e0801/307156/Talin-and-kindlin-team-up-to-regulate-integrin
Article: https://journals.biologists.com/jcs/article/136/8/jcs260746/307144/Talin-and-kindlin-cooperate-to-control-the-density
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Talin and kindlin team up to regulate integrin clustering
Focal adhesions (FAs) are multiprotein complexes that mechanically couple the extracellular matrix (ECM) to the actin cytoskeleton, regulating cell adhesion in response to the external environment. Integrins are a core component of FAs; these are transmembrane receptors that cluster in response to extracellular ligands, a process that is facilitated by the cytoplasmic proteins talin and kindlin. In this study (Pernier et al., 2023), Christophe Le Clainche and colleagues now assess the detailed contributions of talin, kindlin and actomyosin in the process of integrin clustering. Using giant unilamellar vesicles (GUVs), a biomimetic in vitro system, the authors show that talin and kindlin are individually sufficient for clustering integrins. These effects are synergistic, and the presence of both proteins induces the formation of larger integrin clusters. Here, kindlin is able to increase the density of both talin and integrin, whereas talin does not affect density, suggesting kindlin acts upstream of talin. Furthermore, in the presence of talin, kindlin increases integrin segregation in membrane tubes stretched from GUVs by actomyosin contractions, suggesting that kindlin enhances integrin-talin-actomyosin coupling. Overall, this study sheds light on the contributions of talin and kindlin to integrin clustering at FAs, and their role in linking the ECM to actomyosin and thus cell adhesion.
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