Identification of an occludin cell adhesion recognition sequence.
The molecular mechanisms by which the tight junction integral membrane protein, occludin promotes cell adhesion and establishes an endothelial monolayer permeability barrier have not been elucidated. In particular, the amino acid sequences of the occludin cell adhesion recognition (CAR) sites have not been determined. Here we demonstrate that a cyclic peptide containing the sequence LYHY, which is found in the second extracellular domain of occludins in all mammalian species, inhibits the establishment of endothelial cell barriers in vitro and in vivo. This cyclic peptide also prevents the aggregation of fibroblasts stably transfected with cDNA encoding occludin. The data suggest that the LYHY motif is an occludin CAR sequence.
Blaschuk
Orest W
OW
Department of Surgery, Royal Victoria Hospital, Montreal, Quebec, Canada.
Oshima
Tadayuki
T
Gour
Barbara J
BJ
Symonds
J Matthew
JM
Park
Jae H
JH
Kevil
Christopher G
CG
Trocha
Steven D
SD
Michaud
Stephanie
S
Okayama
Naotsuka
N
Elrod
John W
JW
Alexander
J Steven
JS
Sasaki
Makoto
M
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002449:Cell Aggregation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D008833:Microcirculation / Q000187:drug effects; D062793:Occludin; D010446:Peptide Fragments / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568987:Ocln protein, rat; D010446:Peptide Fragments