Open AccessMechanisms of integrin αVβ5 clustering in flat clathrin lattices
Author(s) -
Alba Zuidema,
Wei Wang,
Maaike Kreft,
Lisa te Molder,
Liesbeth Hoekman,
Onno B. Bleijerveld,
Leila Nahidiazar,
Hans Janssen,
Arnoud Sonnenberg
Publication year - 2018
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.221317
Subject(s) - biology , clathrin , integrin , cluster analysis , microbiology and biotechnology , computational biology , evolutionary biology , genetics , endocytosis , receptor , artificial intelligence , computer science
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.