Role of tbc1 in Drosophila embryonic salivary glands

BMC Mol Cell Biol. 2019 Jun 26;20(1):19. doi: 10.1186/s12860-019-0198-z.


Background: 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. 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).

Results: In 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.

Conclusions: These findings support a role for tbc1 in endocytic/membrane trafficking, consistent with its activities in other systems.

Keywords: Apical; Drosophila; Endosome; Golgi; Membrane trafficking; Rab-GAP; Salivary gland.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism
  • Endosomes / metabolism
  • Forkhead Transcription Factors / metabolism
  • GTP Phosphohydrolases / metabolism
  • GTPase-Activating Proteins / genetics*
  • GTPase-Activating Proteins / metabolism*
  • Gene Expression
  • Membrane Transport Proteins / metabolism
  • Monomeric GTP-Binding Proteins / metabolism
  • Open Reading Frames / genetics
  • Optic Lobe, Nonmammalian / metabolism
  • Salivary Glands / embryology*
  • Salivary Glands / metabolism
  • rab GTP-Binding Proteins / metabolism
  • trans-Golgi Network / metabolism


  • Drosophila Proteins
  • Forkhead Transcription Factors
  • GTPase-Activating Proteins
  • Membrane Transport Proteins
  • Tbc1 protein, Drosophila
  • fkh protein, Drosophila
  • GTP Phosphohydrolases
  • Rab8 protein, Drosophila
  • Monomeric GTP-Binding Proteins
  • Rab10 protein, Drosophila
  • rab GTP-Binding Proteins