Extracellular vimentin is sufficient to promote cell attachment, spreading, and motility by a mechanism involving N-acetyl glucosamine-containing structures.

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  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
      Vimentin*/metabolism; Acetylglucosamine/chemistry ; Cell Adhesion ; Cell Movement ; Hyaluronic Acid/chemistry ; Intermediate Filaments/metabolism ; Humans ; Cell Line, Tumor
    • Abstract:
      Vimentin intermediate filaments form part of the cytoskeleton of mesenchymal cells, but under pathological conditions often associated with inflammation, vimentin filaments depolymerize as the result of phosphorylation or citrullination, and vimentin oligomers are secreted or released into the extracellular environment. In the extracellular space, vimentin can bind surfaces of cells and the extracellular matrix, and the interaction between extracellular vimentin and cells can trigger changes in cellular functions, such as activation of fibroblasts to a fibrotic phenotype. The mechanism by which extracellular vimentin binds external cell membranes and whether vimentin alone can act as an adhesive anchor for cells is largely uncharacterized. Here, we show that various cell types (normal and vimentin null fibroblasts, mesenchymal stem cells, and A549 lung carcinoma cells) attach to and spread on polyacrylamide hydrogel substrates covalently linked to vimentin. Using traction force microscopy and spheroid expansion assays, we characterize how different cell types respond to extracellular vimentin. Cell attachment to and spreading on vimentin-coated surfaces is inhibited by hyaluronic acid degrading enzymes, hyaluronic acid synthase inhibitors, soluble heparin or N-acetyl glucosamine, all of which are treatments that have little or no effect on the same cell types binding to collagen-coated hydrogels. These studies highlight the effectiveness of substrate-bound vimentin as a ligand for cells and suggest that carbohydrate structures, including the glycocalyx and glycosylated cell surface proteins that contain N-acetyl glucosamine, form a novel class of adhesion receptors for extracellular vimentin that can either directly support cell adhesion to a substrate or fine-tune the glycocalyx adhesive properties.
      Competing Interests: Conflict of interest The authors declare no conflict of interest with the contents of this article.
      (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Grant Information:
      R35 GM136259 United States GM NIGMS NIH HHS; R35 GM142963 United States GM NIGMS NIH HHS
    • Contributed Indexing:
      Keywords: cell adhesion; cell migration; cytoskeleton; extracellular matrix; glycocalyx; vimentin
    • Accession Number:
      V956696549 (Acetylglucosamine)
      9004-61-9 (Hyaluronic Acid)
      0 (Vimentin)
    • Publication Date:
      Date Created: 20230625 Date Completed: 20230901 Latest Revision: 20230906
    • Publication Date:
      20240829
    • Accession Number:
      PMC10392088
    • Accession Number:
      10.1016/j.jbc.2023.104963
    • Accession Number:
      37356720