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bioRxiv · 10.1101/427112

Mechanisms of integrin αVβ5 clustering in flat clathrin lattices

Zuidema, A.·Wang, W.·Kreft, M.·te Molder, L.·Hoekman, L.·Bleijerveld, O. B.·Nahidiazar, L.·Janssen, H.·Sonnenberg, A.
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Abstract

Summary statementThis article highlights several molecular mechanisms that result in the assembly of integrin V{beta}5-containing flat clathrin lattices in human keratinocytes.\n\nAbstractThe family of integrin transmembrane receptors is essential for the normal function of multicellular organisms by facilitating cell-extracellular matrix adhesion. The vitronectin-binding integrin V{beta}5 localizes to focal adhesions (FAs) as well as poorly characterized flat clathrin lattices (FCLs). Here we show that in human keratinocytes V{beta}5 is predominant found in FCLs and that formation of the V{beta}5-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 {beta}5 and the cytoplasmic domains of {beta}1 or {beta}3, 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 V{beta}5 clustering in FAs. Our findings strongly indicate that clustering of integrin V{beta}5 in FCLs is dictated by the {beta}5 subunit cytoplasmic domain, cellular tension, and recruitment of specific adaptor proteins to the {beta}5 subunit cytoplasmic domains.

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Zuidema, A., Wang, W., Kreft, M., te Molder, L., Hoekman, L., Bleijerveld, O. B., Nahidiazar, L., Janssen, H., Sonnenberg, A.. 2018-09-26. Mechanisms of integrin αVβ5 clustering in flat clathrin lattices. https://doi.org/10.1101/427112

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