Article
- The EMBO Journal (2008) 27, 2077 - 2090
- doi:10.1038/emboj.2008.134
Published online: 17 July 2008
Subject Categories:
Extracellular Alix regulates integrin-mediated cell adhesions and extracellular matrix assembly
Shujuan Pan1, Ruoning Wang1, Xi Zhou1, Joe Corvera2, Malgorzata Kloc3, Richard Sifers4, Gary E Gallick5, Sue-Hwa Lin6 and Jian Kuang1
- Department of Experimental Therapeutics, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA
- A&G Pharmaceuticals Inc., Baltimore, MD, USA
- Immuno-Biology Laboratory, The Methodist Hospital Research Institute, Houston, TX, USA
- Department of Pathology, Baylor College of Medicine, Houston, TX, USA
- Department of Cancer Biology, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA
- Department of Molecular Pathology, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA
Correspondence to:
Jian Kuang, Department of Experimental Therapeutics, MD Anderson Cancer Center, The University of Texas, 1515 Holcombe Blvd., Box 019, Houston, TX 77030, USA. Tel.: +1 713 792 8505; Fax: +1 713 792 3754; E-mail: jkuang@mdanderson.org
Received 16 January 2008; Accepted 19 June 2008
Abstract
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 
5
1-integrin functions. Coating recombinant Alix on the culture substratum for NIH/3T3 cells promotes 51-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.
Keywords:
- Alix,
- extracellular functions,
- fibronectin matrix assembly,
- integrin activation
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