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MBC in Press, published online ahead of print April 11, 2007
Mol. Biol. Cell 10.1091/mbc.E06-08-0744

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Submitted on August 24, 2006
Revised on March 28, 2007
Accepted on April 2, 2007

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,{dagger} Suck-Chei Choi,{ddagger} Kang-Min Lee,{sect} and Chang-Duk Jun*||

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

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 micorvillous ICAM-1 presentation and further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.

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




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