title: RKIKK motif in the intracellular domain is critical for spatial and dynamic organization of ICAM-1: functional implication for the leukocyte adhesion and transmigration.
abstract: 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 ((507)RKIKK(511)) 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 (507)RKIKK(511) 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 (507)RKIKK(511) is an essential motif for the microvillus ICAM-1 presentation and further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: Hyun-Mee
authors.initials: HM
authors.lastname: Oh
authors.forename: SungGa
authors.initials: S
authors.lastname: Lee
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Na
authors.forename: Hyun
authors.initials: H
authors.lastname: Wee
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Suck-Chei
authors.initials: SC
authors.lastname: Choi
authors.forename: Kang-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Chang-Duk
authors.initials: CD
authors.lastname: Jun
mesh_terms: D000199:Actins / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099149:Ezrin
chemical_list: D000199:Actins; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D003598:Cytoskeletal Proteins; D018799:Intercellular Adhesion Molecule-1; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D000099149:Ezrin; C515255:CXCL12 protein, human