RT Journal Article SR Electronic T1 Mechanisms of integrin αVβ5 clustering in flat clathrin lattices JF bioRxiv FD Cold Spring Harbor Laboratory SP 427112 DO 10.1101/427112 A1 Alba Zuidema A1 Wei Wang A1 Maaike Kreft A1 Lisa te Molder A1 Liesbeth Hoekman A1 Onno B. Bleijerveld A1 Leila Nahidiaza A1 Hans Janssen A1 Arnoud Sonnenberg YR 2018 UL http://biorxiv.org/content/early/2018/09/26/427112.abstract AB 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.