Fig. 7.

Models for regulation of core protein levels at junctions by ubiquitylation. (A) Regulation of asymmetry by core protein levels. Green/orange semicircles represent plasma membrane puncta of asymmetrically localised Fz/Stbm complexes. Proximal is to the left and distal to the right. Under normal conditions, feedback loops ensure that Fz is mostly distal, and Stbm is mostly proximal within each cell. An excess of core proteins at junctions driven by loss of Dsh ubiquitylation leads to suboptimal feedback amplification, such that the domain of polarised complexes spreads too far around the cell periphery. Conversely, too little Fmi at junctions results in asymmetric molecular complexes failing to meet and therefore either clustering (feedback caused by positive protein interactions) or mutual inhibition (feedback caused by negative interactions) is abrogated. (B) Regulation of Dsh and Fmi levels by Dbo/Kel and Faf. Dsh is recruited to junctions by Fz and phosphorylated, and this correlates with clustering of asymmetric complexes of the same orientation. Dbo/Kel recognises junctional Dsh, and ubiquitylates excess Dsh leading to its removal from junctions and degradation, most likely by the proteasome (pale blue). Removal of Dsh from junctions also leads to endocytosis of Fmi. An unknown E3 ligase also promotes Fmi internalisation and lysosomal targeting, either by direct ubiquitylation of Fmi (as shown) or of an adaptor protein. Faf normally deubiquitylates some proportion of this internalised Fmi (or a Fmi adaptor) and allows Fmi to be recycled to the plasma membrane.