TY - JOUR
T1 - Role of tbc1 in Drosophila embryonic salivary glands
AU - Johnson, Dorothy M.
AU - Andrew, Deborah J.
N1 - Funding Information:
Funding for this work was provided by the NIH under grant number NIH RO1 DE013899 to DJA and NIH 5F31 DE023721 to DMJ. The funders provided salary support and support for reagents. The funders have no vested interest in the outcomes from this study.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/6/26
Y1 - 2019/6/26
N2 - 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.
AB - 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.
KW - Apical
KW - Drosophila
KW - Endosome
KW - Golgi
KW - Membrane trafficking
KW - Rab-GAP
KW - Salivary gland
UR - http://www.scopus.com/inward/record.url?scp=85068924169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068924169&partnerID=8YFLogxK
U2 - 10.1186/s12860-019-0198-z
DO - 10.1186/s12860-019-0198-z
M3 - Article
C2 - 31242864
AN - SCOPUS:85068924169
SN - 2661-8850
VL - 20
JO - BMC Molecular and Cell Biology
JF - BMC Molecular and Cell Biology
IS - 1
M1 - 19
ER -