RRC ID 21947
Author Strutt H, Searle E, Thomas-Macarthur V, Brookfield R, Strutt D.
Title A Cul-3-BTB ubiquitylation pathway regulates junctional levels and asymmetry of core planar polarity proteins.
Journal Development
Abstract The asymmetric localisation of core planar polarity proteins at apicolateral junctions is required to specify cell polarity in the plane of epithelia. This asymmetric distribution of the core proteins is proposed to require amplification of an initial asymmetry by feedback loops. In addition, generation of asymmetry appears to require the regulation of core protein levels, but the importance of such regulation and the underlying mechanisms is unknown. Here we show that ubiquitylation acts through more than one mechanism to control core protein levels in Drosophila, and that without this regulation cellular asymmetry is compromised. Levels of Dishevelled at junctions are regulated by a Cullin-3-Diablo/Kelch ubiquitin ligase complex, the activity of which is most likely controlled by neddylation. Furthermore, activity of the deubiquitylating enzyme Fat facets is required to maintain Flamingo levels at junctions. Notably, ubiquitylation does not alter the total cellular levels of Dishevelled or Flamingo, but only that of the junctional population. When junctional core protein levels are either increased or decreased by disruption of the ubiquitylation machinery, their asymmetric localisation is reduced and this leads to disruption of planar polarity at the tissue level. Loss of asymmetry by altered core protein levels can be explained by reference to feedback models for amplification of asymmetry.
Volume 140(8)
Pages 1693-702
Published 2013-4-1
DOI 10.1242/dev.089656
PII dev.089656
PMID 23487316
PMC PMC3621487
MeSH Adaptor Proteins, Signal Transducing / metabolism Animals Blotting, Western Cadherins / metabolism Cell Polarity / physiology* Cullin Proteins / metabolism* Dishevelled Proteins Drosophila Drosophila Proteins / metabolism* Endopeptidases / metabolism Epithelial Cells / physiology* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Intercellular Junctions / physiology* Phosphoproteins / metabolism RNA Interference Signal Transduction / physiology* Ubiquitination / physiology*
IF 5.611
Times Cited 31
Drosophila 10254R-1 10254R-2 12799R-2 14739R-1 14739R-2 17030R-1 17030R-2 2574R-2 2574R-3 2924R-3 3473R-2 3473R-7 4443R-1 4443R-2 5440R-3 5823R-1 5823R-3 6303R-1 6303R-2 7375R-2 7375R-3 7425R-1 7425R-2 7656R-2 8188R-1 8188R-2 9602R-2 9602R-3 13343R-4 7828R-2 7828R-3 11861R-1 11861R-2 8711R-1 10752R-1 10752R-3 11275R-1 11275R-3 11514R-1 12236R-1 12857R-2 12857R-3 14260R-4 17068R-1 17068R-4 17156R-1 17156R-2 15802R-1 15802R-3 32491R-1 9343R-1 9343R-3 11082R-2 11082R-3 31160R-1 31160R-3 3711R-2 3711R-3 5319R-3 5319R-4 5186R-1 5186R-2 6224R-1 6224R-3 6384R-1 6765R-1 6765R-2 6792R-2 6792R-3 7058R-1 7058R-3 7230R-2 7230R-4 8060R-1 8069R-2 8411R-2 8411R-3 8924R-1 8924R-2 9426R-2