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.
Mechanisms of integrin αVβ5 clustering in flat clathrin lattices
Present address: Hubrecht Institute, Uppsalalaan 8, Utrecht 3584 CT, The Netherlands
Currently Viewing Accepted Manuscript - Newer Version Available
Alba Zuidema, Wei Wang, Maaike Kreft, Lisa te Molder, Liesbeth Hoekman, Onno B. Bleijerveld, Leila Nahidiazar, Hans Janssen, Arnoud Sonnenberg; Mechanisms of integrin αVβ5 clustering in flat clathrin lattices. J Cell Sci 2018; jcs.221317. doi: https://doi.org/10.1242/jcs.221317
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