page 717, Cohen et al. show that different strengths of the PAR-1 kinase build columnar or liver-like lumens by organizing these microtubule patterns.
Unpolarized epithelia need PAR-1 activity to form lumens. Using RNAi or dominant-negative PAR-1, the authors could prevent lumen generation in both kidney and liver cells and keep microtubules in the radial arrays characteristic of unpolarized cells.
The type of lumen formed depends on the amount of PAR-1 activity. By drastically increasing PAR-1 expression in unpolarized kidney cells, the group created kidney cells with liver-like intercellular lumens and laterally arranged microtubules. Other studies have shown that kidney cells normally pass through such a liver-like phenotype before developing apical lumens. Together, the results suggest that sustained high PAR-1 activity locks liver cells in the liver-like microtubule and lumen arrangement, whereas later lower levels of PAR-1 allow the microtubules in kidney cells to further rearrange to form apical lumens.
Microtubule release from the centrosomes of newly polarizing cells was not affected by the loss of PAR-1, so the kinase probably regulates microtubule capture by the cell cortex. In neurons, PAR-1 phosphorylates the microtubule-associated protein tau, but the group is still searching for the relevant PAR-1 substrates in nonneuronal cells. ▪