Figure 7.

Model Showing Progressive Organization of Core Proteins

(A) Fmi (red) localized apically or laterally is rapidly endocytosed (black arrows), unless it is in an asymmetric junctional complex with Fz (green) or Fz and Stbm (orange). (B) Cytoplasmic proteins Dsh and Dgo (purple and pale blue) or Pk (dark blue) are incorporated into asymmetric complexes, and promote local clustering of complexes of the same orientation by either attractive homophilic interactions or repulsive heterophilic interactions (blue lines and arrows). (C) Locally organized clusters of asymmetric complexes form distinct “puncta” in cell-cell junctions. Cellular asymmetry may be promoted by self-organization of asymmetric complexes within the cell. Individual puncta containing complexes of common polarity increase in size by recruiting further complexes of the same polarity and/or repelling complexes of opposite polarity, leading to local self-enhancement of asymmetric protein distribution (blue arrows). Because intercellular complexes are intrinsically asymmetric, local self-enhancement of Fz clustering in one cell leads to a corresponding enhancement of Stbm clustering in the neighboring cell. This coupled clustering acts as a form of long-range intercellular inhibition (red bars), ensuring that within each cell, domains containing high concentrations of both Fz and Stbm form. Global orientation of such clusters relative to the axes of the tissue is specified by long-range cues, such as distal transport of Fz-containing vesicles (center of cell; Shimada et al. [2006]; Harumoto et al. [2010]).