TY - JOUR T1 - Mechanisms of integrin αVβ5 clustering in flat clathrin lattices JF - bioRxiv DO - 10.1101/427112 SP - 427112 AU - Alba Zuidema AU - Wei Wang AU - Maaike Kreft AU - Lisa te Molder AU - Liesbeth Hoekman AU - Onno B. Bleijerveld AU - Leila Nahidiaza AU - Hans Janssen AU - Arnoud Sonnenberg Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/26/427112.abstract N2 - This article highlights several molecular mechanisms that result in the assembly of integrin αVβ5-containing flat clathrin lattices in human keratinocytes.Abstract The family of integrin transmembrane receptors is essential for the normal function of multicellular organisms by facilitating cell-extracellular matrix adhesion. The vitronectin-binding integrin αVβ5 localizes to focal adhesions (FAs) as well as poorly characterized flat clathrin lattices (FCLs). Here we show that in human keratinocytes αVβ5 is predominant found in FCLs and that formation of the αVβ5-containing FCLs requires the presence of vitronectin as ligand, calcium, and the clathrin adaptor proteins ARH, Numb, and EPS15/EPS15L1. Integrin chimeras, containing the extracellular and transmembrane domains of β5 and the cytoplasmic domains of β1 or β3, almost exclusively localize in FAs. Interestingly, lowering actomyosin-mediated contractility promotes integrin redistribution to FLCs in an integrin tail-dependent manner, while increasing cellular tension favors αVβ5 clustering in FAs. Our findings strongly indicate that clustering of integrin αVβ5 in FCLs is dictated by the β5 subunit cytoplasmic domain, cellular tension, and recruitment of specific adaptor proteins to the β5 subunit cytoplasmic domains. ER -