propagation of destabilization

Rapid disruption of Dishevelled activity uncovers an intercellular role in maintenance of Prickle in core planar polarity protein complexes. Cell Reports, 25: 1415–1424.
Planar polarity, the coordinated polarization of cells in the plane of a tissue, is important for normal tissue development and function. Proteins of the core planar polarity pathway become asymmetrically localized at the junctions between cells to form intercellular complexes that coordinate planar polarity between cell neighbors. Here, we combine tools to rapidly disrupt the activity of the core planar polarity protein Dishevelled, with quantitative measurements of protein dynamics and levels, and mosaic analysis, to investigate Dishevelled function in maintenance of planar polarity. We provide mechanistic insight into the hierarchical relationship of Dishevelled with other members of the core planar polarity complex. Notably, we show that removal of Dishevelled in one cell causes rapid release of Prickle into the cytoplasm in the neighboring cell. This release of Prickle generates a self-propagating wave of planar polarity complex destabilization across the tissue. Thus, Dishevelled actively maintains complex integrity across intercellular junctions.

PCP（Planar Cell Polarity）は、細胞内で６つのcore componentがproximal-distal axisに沿って平面内で非対称に分布し、隣接細胞間の細胞膜上でprotein complexを形成することにより制御されている。こうして書くとなんやらよく分からんけど、図を見れば一目瞭然。この論文では、このcore PCP protein complexの一つ、Dishevelled（Dsh）のactivityが阻害されると、隣接細胞側のPrickle（Pk）が細胞膜上のcomplexから外れてしまい、この細胞質中に出たPkが同細胞内で反対側に位置するcomplexのDshをdestabilizeする。これがまた隣の細胞でPkを外してしまうことになり、ということで、PCP complexの不安定化は連鎖的にどんどん周囲の細胞へ伝播してしまうことになる。
実は、こないだ申請書に書いていた自分の仮説の一つが、このメカニズムでキレイに説明できそうなのでちょっと感動したのだった。