Integrins are formed through heterodimerisation of α and β subunits. Depending on the combination of these subunits, they recognise different components of the extracellular matrix, such as laminins, collagens and fibronectin. The vitronectin-binding integrin αVβ5 localises to focal adhesions (FAs), but also to flat clathrin lattices (FCLs; also described as clathrin ‘plaques’) – poorly characterised clathrin structures that are distinct from clathrin-coated pits. Now, Arnoud Sonnenberg and colleagues (Zuidema et al., 2018) investigate the mechanisms that control the localisation of αVβ5 to FCLs in human keratinocytes. The authors first demonstrate, using human keratinocytes, that the formation of αVβ5-containing FCLs requires the binding of αVβ5 to its ligand vitronectin in the presence of Ca2+. Furthermore, the clustering of αVβ5 in FCLs is mediated by the clathrin adaptor proteins ARH, Numb and EPS15/EPS15L1, but only when actomyosin-driven cellular tension is low. In addition, the authors construct integrin chimeras, and demonstrate that they have an altered localisation pattern and cluster predominantly in FAs, but switch to FCLs when cellular tension is reduced. These data demonstrate that integrin clustering in different adhesion structures depends on adaptor protein recruitment and is mediated by the magnitude of force exerted on the integrins.
