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Role of tbc1 in Drosophila embryonic salivary glands

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...

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Autores principales: Johnson, Dorothy M., Andrew, Deborah J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595604/
https://www.ncbi.nlm.nih.gov/pubmed/31242864
http://dx.doi.org/10.1186/s12860-019-0198-z
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author Johnson, Dorothy M.
Andrew, Deborah J.
author_facet Johnson, Dorothy M.
Andrew, Deborah J.
author_sort Johnson, Dorothy M.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12860-019-0198-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-65956042019-07-11 Role of tbc1 in Drosophila embryonic salivary glands Johnson, Dorothy M. Andrew, Deborah J. BMC Mol Cell Biol Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12860-019-0198-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-26 /pmc/articles/PMC6595604/ /pubmed/31242864 http://dx.doi.org/10.1186/s12860-019-0198-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Johnson, Dorothy M.
Andrew, Deborah J.
Role of tbc1 in Drosophila embryonic salivary glands
title Role of tbc1 in Drosophila embryonic salivary glands
title_full Role of tbc1 in Drosophila embryonic salivary glands
title_fullStr Role of tbc1 in Drosophila embryonic salivary glands
title_full_unstemmed Role of tbc1 in Drosophila embryonic salivary glands
title_short Role of tbc1 in Drosophila embryonic salivary glands
title_sort role of tbc1 in drosophila embryonic salivary glands
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595604/
https://www.ncbi.nlm.nih.gov/pubmed/31242864
http://dx.doi.org/10.1186/s12860-019-0198-z
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