Article

L-selectin: Mechanisms and physiological significance of ectodomain cleavage

Cardiovascular Research Center and Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, 22908-1294, USA.
Journal of Cellular and Molecular Medicine (Impact Factor: 3.7). 04/2005; 9(2):255-66. DOI: 10.1111/j.1582-4934.2005.tb00354.x
Source: PubMed

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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Available from: Klaus Ley, Jul 28, 2015
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    • "Following cellular activation, leukocytes increase expression of L-selectin, which is then shed by proteolytic cleavage into a soluble form that inhibits leukocyte adhesion, and hence modulates the speed of leukocyte rolling (Hafezi-Moghadam et al., 2001; Smalley and Ley, 2005). Selectins bind to specific ligands through weak interactions, which enable leukocytes to roll on endothelium; among them, the P-selectin glycoprotein ligand-1 (PSGL-1), constitutively expressed by leukocytes, binds all three members of the selectin family (Moore, 1998). "
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