Tight junctions (top) disassemble without Par-3 (middle) but are rescued by active cofilin (bottom).

On page 671, Chen and Macara unveil a mechanism by which Par-3 orchestrates cell polarization by regulating actin reorganization.

Par-3 is one member of an apical polarity-inducing complex that also includes Par-6 and aPKC. The Par proteins are well-known for protein–protein interactions, but how these interactions lead to polarization is less clear. Using RNAi, Chen and Macara had previously shown that Par-3 helps assemble tight junctions (TJs) in epithelial cells by inhibiting an activator of Rac. The study now reveals a second function of Par-3 at TJs.

In the previous work, the authors saw that TJ formation required actin reorganization, so Chen looked for any effects of Par-3 on actin regulators. He now finds that cofilin, an actin filament severing protein, is phosphorylated and thus inactivated in the absence of Par-3.

The inactivation of cofilin in the Par-3 RNAi cells is due to overactive LIMK2, which is one of several kinases that modifies cofilin. Par-3 binds to LIMK2 and inhibits its kinase activity. By doing so at TJs, where the Par complex is localized, Par-3 would keep cofilin active, thus driving actin reorganization.

Par-3 and LIMK2 are widely expressed, so Chen suspects that actin might be regulated by these proteins in other cell types. He is currently examining whether migrating cells require Par-3 to block LIMK2 at the leading edge, where actin turnover is needed.