Cell polarity proteins regulate tight junction formation and directional migration in epithelial cells. To date, the mechanism by which these polarity proteins assemble at the leading edge of migrating epithelial cells remains unclear. We report that occludin, a transmembrane protein, is localized at the leading edge of migrating cells and regulates directional cell migration. During migration, occludin knockdown disrupted accumulation of aPKC-Par3 and PATJ at the leading edge, 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 alpha to the leading edge via association with its C-terminal SH2 domain. Loss of occludin attenuated activation of PI3K, leading to disorganization of the actin cytoskeleton and reduced cell protrusions. Our data indicate 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.

We develop a general testing scenario for probabilistic processes, giving rise to two theories: probabilistic may testing and probabilistic must testing. These are applied to a simple probabilistic version of the process calculus CSP. We examine the algebraic theory of probabilistic testing, and show that many of the axioms of standard testing are no longer valid in our probabilistic setting; even for non-probabilistic CSP processes, the distinguishing power of probabilistic tests is much greater than that of standard tests. We develop a method for deriving inequations valid in probabilistic may testing based on a probabilistic extension of the notion of simulation. Using this, we obtain a complete axiomatisation for non-probabilistic processes subject to probabilistic may testing.