The metalloprotease ADAM8 is associated with and regulates the function of the adhesion receptor PSGL-1 through ERM proteins

Authors

  • Maria Domínguez-Luis,

    1. Servicio de Reumatología, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain
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  • Amalia Lamana,

    1. Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain
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  • Jesús Vazquez,

    1. Centro de Biología Molecular Severo Ochoa, C.S.I.C., Cantoblanco, Campus de la Universidad Autónoma de Madrid, Madrid, Spain
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  • Rósula García-Navas,

    1. Centro de Investigación del Cáncer, Instituto de Biología Celular y Molecular del Cáncer, Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain
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  • Faustino Mollinedo,

    1. Centro de Investigación del Cáncer, Instituto de Biología Celular y Molecular del Cáncer, Consejo Superior de Investigaciones Científicas-Universidad de Salamanca, Salamanca, Spain
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  • Francisco Sánchez-Madrid,

    1. Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain
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  • Federico Díaz-González,

    1. Servicio de Reumatología, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain
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    • These authors contributed equally to this work.

  • Ana Urzainqui

    Corresponding author
    1. Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, Madrid, Spain
    • Servicio de Inmunología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa, C/ Diego de León, 28006 Madrid, Spain Fax: +91-5202374
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    • These authors contributed equally to this work.


Abstract

The P-selectin glycoprotein ligand-1 (PSGL-1) is involved in the initial contact of leukocytes with activated endothelium, and its adhesive function is regulated through its proteolytic processing. We have found that the metalloprotease ADAM8 is both associated with PSGL-1 through the ezrin–radixin–moesin actin-binding proteins and able to cause the proteolytic cleavage of this adhesion receptor. Accordingly, ADAM8 knockdown increases PSGL-1 expression, and functional assays show that ADAM8 is able to reduce leukocyte rolling on P-selectin and hence on activated endothelial cells. We conclude that ADAM8 modulates the expression and function of PSGL-1.

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