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© The Rockefeller University Press, 0021-9525/1997//563 $5.00
The Journal of Cell Biology, Volume 139, Number 2, , 1997 563-571


Article

Presentation of Integrins on Leukocyte Microvilli: A Role for the Extracellular Domain in Determining Membrane Localization



M. Abi Abitorabi, Russell K. Pachynski, Ronald E. Ferrando, Mark Tidswell, and David J. Erle

The Lung Biology Center, Department of Medicine, University of California, San Francisco, California 94143

Adhesion of blood leukocytes to the endothelium involves multiple steps including initial attachment (tethering), rolling, and firm arrest. Presentation of adhesion molecules on leukocyte microvilli can substantially enhance tethering. Localization of L-selectin to microvilli and of CD44 to the planar cell body have been shown to depend upon their transmembrane and cytoplasmic domains. We investigated the role of leukocyte integrin transmembrane and cytoplasmic domains in initiating adhesion under flow and in microvillous localization. Integrins {alpha}4β7, {alpha}Lβ2, and {alpha}Mβ2 were heterologously expressed in K562 cells. {alpha}4β7 initiated adhesion under flow and localized to microvilli, whereas β2 integrins did not initiate adhesion and localized to the cell body. Chimeric integrins were produced by replacing the {alpha}4β7 cytoplasmic and/or transmembrane domains with the homologous domains of {alpha}Lβ2 or {alpha}Mβ2. Unexpectedly, these chimeras efficiently mediated adhesion to the {alpha}4β7 ligand mucosal addressin cell adhesion molecule–1 under flow and localized to microvilli. Therefore, differences between the transmembrane and cytoplasmic domains of {alpha}4 and β2 integrins do not account for differences in ability to support attachment under flow or in membrane localization. Integrins {alpha}4β1, {alpha}5β1, {alpha}6Aβ1, {alpha}vβ3, and {alpha}Eβ7 also localized to microvilli. Transmembrane proteins known or suspected to associate with extracellular domains of microvillous integrins, including tetraspans and CD47, were concentrated on microvilli as well. These findings suggest that interactions between the extracellular domains of integrins and associated proteins could direct the assembly of multimolecular complexes on leukocyte microvilli.


Abbreviations used in this paper: ICAM-1, intercellular adhesion molecule–1; MAdCAM-1, mucosal addressin cell adhesion molecule–1; VCAM-1, vascular cell adhesion molecule–1.

Address all correspondence to M. Abi Abitorabi, University of California, San Francisco, Box 0854, San Francisco, CA 94143-0854. Tel.: (415) 206-6649. Fax: (415) 206-4123.



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