Dynamic association of L-selectin with the lymphocyte cytoskeletal matrix

Sharon S. Evans, David M. Schleider, Lori A. Bowman, Michelle L. Francis, Geoffrey S. Kansas, Jennifer D. Black

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

L-selectin mediates lymphocyte extravasation into lymphoid tissues through binding to sialomucin-like receptors on the surface of high endothelial venules (HEV). This study examines the biochemical basis and regulation of interactions between L-selectin, an integral transmembrane protein, and the lymphocyte cytoskeleton. Using a detergent-based extraction procedure, constitutive associations between L-selectin and the insoluble cytoskeletal matrix could not be detected. However, engagement of the L- selectin lectin domain by Abs or by glycosylation-dependent cell adhesion molecule-1, an HEV-derived ligand for L-selectin, rapidly triggered redistribution of L-selectin to the detergent-insoluble cytoskeleton. L- selectin attachment to the cytoskeleton was not prevented by inhibitors of actin/microtubule polymerization (cytochalasin B, colchicine, or nocodozole) or serine/threonine and tyrosine kinase activity (staurosporine, calphostin C, or genistein), although L-selectin-mediated adhesion of human PBL was markedly suppressed by these agents. Exposure of human PBL or murine pre-B transfectants expressing full-length human L-selectin to fever-range hyperthermia also markedly increased L-selectin association with the cytoskeleton, directly correlating with enhanced L-selectin-mediated adhesion. In contrast, a deletion mutant of L-selectin lacking the COOH- terminal 11 amino acids failed to associate with the cytoskeletal matrix in response to Ab cross-linking or hyperthermia stimulation and did not support adhesion to HEV. These studies, when taken together with the previously demonstrated interaction between the L-selectin cytoplasmic domain and the cytoskeletal linker protein α-actinin, strongly implicate the actin-based cytoskeleton in dynamically controlling L-selectin adhesion.

Original languageEnglish (US)
Pages (from-to)3615-3624
Number of pages10
JournalJournal of Immunology
Volume162
Issue number6
StatePublished - Mar 15 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Evans, S. S., Schleider, D. M., Bowman, L. A., Francis, M. L., Kansas, G. S., & Black, J. D. (1999). Dynamic association of L-selectin with the lymphocyte cytoskeletal matrix. Journal of Immunology, 162(6), 3615-3624.