The Tight Junction Protein, Occludin, Regulates the Directional Migration of Epithelial Cells

On Feb 15, 2010, Prof. Zhengjun Chen´s group from the Institute of Biochemistry and Cell Biology published a research article entitled "The Tight Junction Protein, Occludin, Regulates the Directional Migration of Epithelial Cells" in Developmental Cell. This work was carried out by Dr. Dan Du under the supervision of Prof. Zhengjun Chen.

 

Although cell polarity proteins are known to regulate tight junction formation and directional migration in epithelial cells, the mechanism by which these polarity proteins assemble at the leading edge of migrating epithelial cells remains unclear. In this paper, the authors reported that occludin, a transmembrane protein, was localized at the leading edge of migrating cells and regulated directional cell migration. Occludin knockdown disrupted accumulation of aPKC-Par3 and PATJ at the leading edge during migration, and led to a disorganized microtubule network and defective reorientation of the microtubule organization center (MTOC). Phosphorylation of occludin at tyrosine 473 residue allowed recruitment of p85 to the leading edge via association with its C-terminal SH2 domain. Loss of occludin attenuated activation of PI3K, and resulted in disorganization of the actin cytoskeleton and reduced cell protrusions. These data indicates that occludin is required for the leading-edge localization of polarity proteins, aPKC-Par3 and PATJ, and promotes cell protrusion by regulating membrane-localized activation of PI3K.