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Extracellular Alix regulates integrin‐mediated cell adhesions and extracellular matrix assembly
Author(s) -
Pan Shujuan,
Wang Ruoning,
Zhou Xi,
Corvera Joe,
Kloc Malgorzata,
Sifers Richard,
Gallick Gary E,
Lin SueHwa,
Kuang Jian
Publication year - 2008
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2008.134
Subject(s) - extracellular matrix , biology , extracellular , microbiology and biotechnology , integrin , cell adhesion , cell , biochemistry
Alix (ALG‐2‐interacting protein X), a cytoplasmic adaptor protein involved in endosomal sorting and actin cytoskeleton assembly, is required for the maintenance of fibroblast morphology. As Alix has sequence similarity to adhesin in Entamoeba histolytica , and we observed that Alix is secreted, we determined whether extracellular Alix affects fibroblast morphology. Here, we demonstrate that secreted Alix is deposited on the substratum of non‐immortalized WI38 fibroblasts. Antibody binding to extracellular Alix retards WI38 cell adhesion and spreading on fibronectin and vitronectin. Alix knockdown in WI38 cells reduces spreading and fibronectin assembly, and the effect is partially complemented by coating recombinant Alix on the cell substratum. Immortalized NIH/3T3 fibroblasts deposit less Alix on the substratum and have defects in α 5 β 1 ‐integrin functions. Coating recombinant Alix on the culture substratum for NIH/3T3 cells promotes α 5 β 1 ‐integrin‐mediated cell adhesions and fibronectin assembly, and these effects require the aa 605–709 region of Alix. These findings demonstrate that a sub‐population of Alix localizes extracellularly and regulates integrin‐mediated cell adhesions and fibronectin matrix assembly.