L-selectin: mechanisms and physiological significance of ectodomain cleavage.
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.
Smalley
D M
DM
Cardiovascular Research Center and Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, 22908-1294, USA.
Ley
K
K
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007962:Leukocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D008666:Metalloendopeptidases / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid
D008565:Membrane Proteins; D019041:L-Selectin; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human