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Mechanisms of integrin αVβ5 clustering in flat clathrin lattices.

Journal of cell science (2018-10-12)
Alba Zuidema, Wei Wang, Maaike Kreft, Lisa Te Molder, Liesbeth Hoekman, Onno B Bleijerveld, Leila Nahidiazar, Hans Janssen, Arnoud Sonnenberg
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 predominantly found in FCLs, and formation of the αVβ5-containing FCLs requires the presence of vitronectin as ligand, Ca2+, and the clathrin adaptor proteins ARH (also known as LDLRAP1), 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-ITSN1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Biotin, ≥99% (HPLC), lyophilized powder
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Anti-Fibronectin antibody, Mouse monoclonal, clone FN-15, purified from hybridoma cell culture