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Vol. 18, Issue 6, 2322-2335, June 2007

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RKIKK Motif in the Intracellular Domain Is Critical for Spatial and Dynamic Organization of ICAM-1: Functional Implication for the Leukocyte Adhesion and Transmigration

Hyun-Mee Oh^*, SungGa Lee^*, Bo-Ra Na^*, Hyun Wee^*, Sang-Hyun Kim, Suck-Chei Choi, Kang-Min Lee, and Chang-Duk Jun^*,||

*Department of Life Science, and ^||Research Center for Biomolecular Nanotechnology, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea; Department of Pharmacology, Kyungpook National University, Daegu 700-422, Korea; Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, Korea; and Division of Biological Sciences, College of Natural Science, Chonbuk National University, Jeonju, Chonbuk 561-756, Korea

Submitted August 24, 2006; Revised March 28, 2007; Accepted April 2, 2007
Monitoring Editor: Yu-li Wang

No direct evidence has been reported whether the spatial organization of ICAM-1 on the cell surface is linked to its physiological function in terms of leukocyte adhesion and transendothelial migration (TEM). Here we observed that ICAM-1 by itself directly regulates the de novo elongation of microvilli and is thereby clustered on the microvilli. However, truncation of the intracellular domain resulted in uniform cell surface distribution of ICAM-1. Mutation analysis revealed that the C-terminal 21 amino acids are dispensable, whereas a segment of 5 amino acids (⁵⁰⁷RKIKK⁵¹¹) in the NH-terminal third of intracellular domain, is required for the proper localization and dynamic distribution of ICAM-1 and the association of ICAM-1 with F-actin, ezrin, and moesin. Importantly, deletion of the ⁵⁰⁷RKIKK⁵¹¹ significantly delayed the LFA-1–dependent membrane projection and decreased leukocyte adhesion and subsequent TEM. Endothelial cells treated with cell-permeant penetratin-ICAM-1 peptides comprising ICAM-1 RKIKK sequences inhibited leukocyte TEM. Collectively, these findings demonstrate that ⁵⁰⁷RKIKK⁵¹¹ is an essential motif for the microvillus ICAM-1 presentation and further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Chang-Duk Jun (cdjun{at}gist.ac.kr)

Abbreviations used: EPI, epifluorescence; ERM, ezrin/radixin/moesin; ERMBMP, ERM-binding membrane proteins; HUVECs, human umbilical vascular endothelial cells; IgSF, Ig superfamily; PBL, peripheral blood lymphocyte; TEM, transendothelial migration.