• Open Access

L-selectin: mechanisms and physiological significance of ectodomain cleavage

Authors

  • D. M. Smalley,

    Corresponding author
    1. Cardiovascular Research Center and Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
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  • K. Ley

    1. Cardiovascular Research Center and Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, USA
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*Correspondence to: Dr. Klaus LEY, M.D., Cardiovascular Research Center, MR5 Bldg., Room 1013 P. O. Box 801394, Charlottesville, VA 22908–1294, USA. Tel.: 434-924-9966 Fax.:434-924-2828 E-mail: kfl3f@virginia.edu

Abstract

L-selectin is a cell adhesion molecule consisting of a large, highly glycosylated, extracellular domain, a single spanning transmembrane domain and a small cytoplasmic tail. It is expressed on most leukocytes and is involved in their rolling on inflamed vascular endothelium prior to firm adhesion and transmigration. It is also required for the constitutive trafficking of lymphocytes through secondary lymphoid organs. Like most adhesion molecules, L-selectin function is regulated by a variety of mechanisms including gene transcription, post-translational modifications, association with the actin cytoskeleton, and topographic distribution. In addition, it is rapidly downregulated by proteolytic cleavage near the cell surface by ADAM-17 (TACE) and at least one other “sheddase”. This process of “ectodomain shedding” results in the release of most of the extracellular portion of L-selectin from the cell surface while retaining the cytoplasmic, transmembrane, and eleven amino acids of the extracellular domain on the cell. This review will examine the mechanism(s) of L-selectin ectodomain shedding and discuss the physiological implications.

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