Authors
M Zoltner2; K F Leung1; R C del Pino2; D Horn2; M C Field2; 1 Department of Pathology, University of Cambridge, Cambridge; 2 Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee Discussion
We have demonstrated that ubiquitylation pathways play a crucial role in modulating the surface architecture of bloodstream-form Trypanosoma brucei. The deubiquitylating enzyme TbUsp7 controls the abundance of a precise cohort of membrane proteins, including invariant surface glycoprotein ISG75 and the acid phosphatase MBAP1, that is required for endocytosis and exocytosis. Recently we discovered a functional link between TbUsp7 and the conserved cullin adaptor TbSkp1, the mammalian orthologue of which is part of the Skp1-Fbox-Cullin1-Rbx1 complex. Both TbSkp1 and TbUsp7 silencing blocked endocytosis and the impacts on the global proteome were highly similar. Additionally, TbSkp1 knockdown dramatically decreased TbUsp7 abundance. These findings add a cullin RING ligase to this ubiquitylation pathway critical for controlling surface protein composition and affecting suramin sensitivity. 
