PL-04 Regulation of self-renewal, proliferation and differentiation in an adult stem cell lineage

to connect cells together is ‘‘adherens junction (AJ)’’, which comprises cadherin receptors, associated proteins termed catenins, and cytoskeletons. The cadherin–catenin complex interacts with actin filaments via a-catenin. Recent analysis identified linkers between a-catenin and F-actin. The presence or absence of such linkers can alter the morphology of cell junctions, epithelial or mesenchymal, suggesting that they might function as a modulator for junctional shapes, in turn for the morphology of cell mass. The AJ-actin linkage is also important for constricting the apical surface of epithelial cells via ROCK-dependent phosphorylation of myosin light chain, a process important for cell sheet bending. We also found that the AJs are linked with microtubules: one of the catenins, p120, binds PLEKHA7 and in turn Nezha. Nezha then tethers microtubules to the AJ via their minus-ends, as if Nezha is functioning as a microtubule-organizing center. KIFC3, a minusend directed kinesin motor, seems to interact with the AJs via these microtubules. This KIFC3-dependent system appears to be important for the integrity of AJs, as depletion of these molecules impair AJ assembly. Thus, the AJs can be remodeled through the interactions not only with actin cables but also with microtubules. Identification of developmental signaling pathways to regulate these AJ-cytoskeletal interactions should facilitate our deeper understanding of morphogenetic mechanisms.