Abstract
BackgroundCG4552/tbc1 was identified as a downstream target of Fork head (Fkh), the single Drosophila member of the FoxA family of transcription factors and a major player in salivary gland formation and homeostasis. Tbc1 and its orthologues have been implicated in phagocytosis, the innate immune response, border cell migration, cancer and an autosomal recessive form of non-degenerative Pontocerebellar hypoplasia. Recently, the mammalian Tbc1 orthologue, Tbc1d23, has been shown to bind both the conserved N-terminal domains of two Golgins (Golgin-97 and Golgin-245) and the WASH complex on endosome vesicles. Through this activity, Tbc1d23 has been proposed to link endosomally-derived vesicles to their appropriate target membrane in the trans Golgi (TGN).ResultsIn this paper, we provide an initial characterization of Drosophila orthologue, we call tbc1. We show that, like its mammalian orthologue, Tbc1 localizes to the trans Golgi. We show that it also colocalizes with a subset of Rabs associated with both early and recycling endosomes. Animals completely missing tbc1 survive, but females have fertility defects. Consistent with the human disease, loss of tbc1 reduces optic lobe size and increases response time to mechanical perturbation. Loss and overexpression of tbc1 in the embryonic salivary glands leads to secretion defects and apical membrane irregularities.ConclusionsThese findings support a role for tbc1 in endocytic/membrane trafficking, consistent with its activities in other systems.
Highlights
CG4552/tbc1 was identified as a downstream target of Fork head (Fkh), the single Drosophila member of the FoxA family of transcription factors and a major player in salivary gland formation and homeostasis
Based on the requirements for tbc1 function in neurite outgrowth, for the engulfment of bacteria by Drosophila S2 cells, and in the formation of a uniform and smooth apical membrane in Drosophila salivary gland (SG), we propose that Tbc1 functions to regulate vesicular trafficking for localized membrane expansion
Many genes linked to vesicular transport were identified in the same S2 RNA interference (RNAi) screen that linked the loss of tbc1 to reduced phagocytosis [14]
Summary
CG4552/tbc was identified as a downstream target of Fork head (Fkh), the single Drosophila member of the FoxA family of transcription factors and a major player in salivary gland formation and homeostasis. The mammalian Tbc orthologue, Tbc1d23, has been shown to bind both the conserved N-terminal domains of two Golgins (Golgin-97 and Golgin-245) and the WASH complex on endosome vesicles. Through this activity, Tbc1d23 has been proposed to link endosomally-derived vesicles to their appropriate target membrane in the trans Golgi (TGN). Epithelial tubes comprise a monolayer of tightly-adherent and polarized cells surrounding a central lumen. There is an outer layer of supporting cells, such as the myoepithelial cells, which form the layer of smooth muscle that surrounds many secretory organs [2]. The basic organization of epithelial tubes is shared, each tubular organ has a unique architecture linked to its primary function. For example, the morphological differences between the aorta (a simple tube with relatively few side branches), which functions primarily in blood transport, and the lungs (highlybranched anastomosing tubes), which need large surface areas for gas exchange
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