Abstract
The core planar polarity proteins are required to specify the orientation of structures that are polarised in the plane of the epithelium. In the Drosophila melanogaster wing, the core proteins localise asymmetrically at either proximal or distal cell edges. Asymmetric localisation is thought to be biased by long-range cues, causing asymmetric complexes to become aligned with the tissue axes. Core proteins are then thought to participate in feedback interactions that are necessary to amplify asymmetry, and in order for such feedback interactions to operate correctly, the levels of the core proteins at junctions must be tightly regulated. We have investigated regulation of the core protein Prickle (Pk) in the pupal wing. The core protein Strabismus (Stbm) is required to recruit Pk into asymmetric complexes at proximal cell ends, and we report here that it also promotes proteasomal degradation of excess Pk, probably via a Cullin-1 dependent process. We also show for the first time that Pk is farnesylated in vivo, and this is essential for Pk function in the wing. Notably, farnesylation of Pk is necessary for it to be recruited into asymmetric complexes and function in feedback amplification, probably by reinforcing weak direct interactions between Stbm and Pk. Furthermore, farnesylation is also required for Stbm to promote proteasomal degradation of Pk. We propose that Stbm recruits farnesylated Pk into asymmetric complexes, but also promotes degradation of excess Pk that would otherwise perturb feedback amplification.
Highlights
The Prickle (Pk) protein is one of the ‘‘core’’ planar polarity proteins which are necessary to polarise cells in the plane of epithelia in Drosophila melanogaster and vertebrates [1,2,3]
Treatment of prepupal wings with MG132 to block proteasomal degradation caused a substantial increase in Pk levels (Figure 1D,E), consistent with Pk normally being rapidly degraded in the proteasome
One possibility is that if Pk forms asymmetric complexes with Stbm and other core proteins, it is protected from degradation, but if Pk is pkDCaaX (F)
Summary
The Prickle (Pk) protein is one of the ‘‘core’’ planar polarity proteins which are necessary to polarise cells in the plane of epithelia in Drosophila melanogaster and vertebrates [1,2,3]. Fmi and Stbm appear to assemble into an intrinsically asymmetric intercellular complex that couples adjacent cells, and Pk and the other cytoplasmic core proteins (Dsh and Dgo) are thought to organise intercellular complexes of the same polarity into discrete membrane domains at the proximal and distal cell edges [4]. This redistribution can be explained by feedback models, consisting of either positive (stabilising) interactions between complexes in the same orientation or negative (destabilising) interactions between complexes in opposite orientations [4,5,6]
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