Extracellular Alix regulates integrin-mediated cell adhesions and extracellular matrix assembly

Shujuan Pan, Ruoning Wang, Xi Zhou, Joe Corvera, Malgorzata Kloc, Richard Sifers, Gary E. Gallick, Sue Hwa Lin, Jian Kuang

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 α5β1-integrin functions. Coating recombinant Alix on the culture substratum for NIH/3T3 cells promotes α 5β1-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.

Original languageEnglish (US)
Pages (from-to)2077-2090
Number of pages14
JournalEMBO Journal
Issue number15
StatePublished - Aug 6 2008


  • Alix
  • Extracellular functions
  • Fibronectin matrix assembly
  • Integrin activation

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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