Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs

Claus‐Werner Franzke, Kaisa Tasanen, Heike Schäcke, Zhongjun Zhou, Karl Tryggvason, Cornelia Mauch, Paola Zigrino, Susan Sunnarborg, David C. Lee, Falk Fahrenholz, Leena Bruckner‐Tuderman

Author Affiliations

  1. Claus‐Werner Franzke1,
  2. Kaisa Tasanen2,
  3. Heike Schäcke1,
  4. Zhongjun Zhou3,
  5. Karl Tryggvason3,
  6. Cornelia Mauch4,
  7. Paola Zigrino4,
  8. Susan Sunnarborg5,
  9. David C. Lee5,
  10. Falk Fahrenholz6 and
  11. Leena Bruckner‐Tuderman*,1
  1. 1 Department of Dermatology, University of Münster, D‐48149, Münster, Germany
  2. 2 Department of Dermatology, University of Oulu, F‐90220, Oulu, Finland
  3. 3 Karolinska Institute, Division of Matrix Biology, S‐17177, Stockholm, Sweden
  4. 4 Department of Dermatology, University of Cologne, D‐50931, Cologne, Germany
  5. 5 Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599‐7260, USA
  6. 6 Institute of Biochemistry, University of Mainz, D‐55128, Mainz, Germany
  1. *Corresponding author. E-mail: tuderma{at}
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Collagen XVII, a type II transmembrane protein and epithelial adhesion molecule, can be proteolytically shed from the cell surface to generate a soluble collagen. Here we investigated the release of the ectodomain and identified the enzymes involved. After surface biotinylation of keratinocytes, the ectodomain was detectable in the medium within minutes and remained stable for >48 h. Shedding was enhanced by phorbol esters and inhibited by metalloprotease inhibitors, including hydroxamates and TIMP‐3, but not by inhibitors of other protease classes or by TIMP‐2. This profile implicated MMPs or ADAMs as candidate sheddases. MMP‐2, MMP‐9 and MT1‐MMP were excluded, but TACE, ADAM‐10 and ADAM‐9 were shown to be expressed in keratinocytes and to be actively involved. Transfection with cDNAs for the three ADAMs resulted in increased shedding and, vice versa, in TACE‐deficient cells shedding was significantly reduced, indicating that transmembrane collagen XVII represents a novel class of substrates for ADAMs. Functionally, release of the ectodomain of collagen XVII from the cell surface was associated with altered keratinocyte motility in vitro.

  • Received January 9, 2002.
  • Revision received July 24, 2002.
  • Accepted August 15, 2002.
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