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Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability
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| Zeitschriftentitel: | Development |
|---|---|
| Personen und Körperschaften: | , , , , , |
| In: | Development, 137, 2010, 9, S. 1493-1503 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The Company of Biologists
|
| Schlagwörter: |
| author_facet |
Duchi, Serena Fagnocchi, Luca Cavaliere, Valeria Hsouna, Anita Gargiulo, Giuseppe Hsu, Tien Duchi, Serena Fagnocchi, Luca Cavaliere, Valeria Hsouna, Anita Gargiulo, Giuseppe Hsu, Tien |
|---|---|
| author |
Duchi, Serena Fagnocchi, Luca Cavaliere, Valeria Hsouna, Anita Gargiulo, Giuseppe Hsu, Tien |
| spellingShingle |
Duchi, Serena Fagnocchi, Luca Cavaliere, Valeria Hsouna, Anita Gargiulo, Giuseppe Hsu, Tien Development Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability Developmental Biology Molecular Biology |
| author_sort |
duchi, serena |
| spelling |
Duchi, Serena Fagnocchi, Luca Cavaliere, Valeria Hsouna, Anita Gargiulo, Giuseppe Hsu, Tien 1477-9129 0950-1991 The Company of Biologists Developmental Biology Molecular Biology http://dx.doi.org/10.1242/dev.042804 <jats:p>Mutations in the human von Hippel-Lindau (VHL) genes are the cause of VHL disease, which displays multiple benign and malignant tumors. The VHL gene has been shown to regulate angiogenic potential and glycolic metabolism via its E3 ubiquitin ligase function against the alpha subunit of hypoxia-inducible factor (HIF). However, many other HIF-independent functions of VHL have been identified and recent evidence indicates that the canonical function cannot fully explain the VHL mutant cell phenotypes. Many of these functions have not been verified in genetically tractable systems. Using an established follicular epithelial model in Drosophila, we show that the Drosophila VHL gene is involved in epithelial morphogenesis via stabilizing microtubule bundles and aPKC. Microtubule defects in VHL mutants lead to mislocalization of aPKC and subsequent loss of epithelial integrity. Destabilizing microtubules in ex vivo culture of wild-type egg chambers can also result in aPKC mislocalization and epithelial defects. Importantly, paclitaxel-induced stabilization of microtubules can rescue the aPKC localization phenotype in Drosophila VHL mutant follicle cells. The results establish a developmental function of the VHL gene that is relevant to its tumor-suppressor activity.</jats:p> <i>Drosophila VHL</i> tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability Development |
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10.1242/dev.042804 |
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The Company of Biologists, 2010 |
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| title |
Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_unstemmed |
Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_full |
Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_fullStr |
Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_full_unstemmed |
Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_short |
Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_sort |
<i>drosophila vhl</i> tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and apkc stability |
| topic |
Developmental Biology Molecular Biology |
| url |
http://dx.doi.org/10.1242/dev.042804 |
| publishDate |
2010 |
| physical |
1493-1503 |
| description |
<jats:p>Mutations in the human von Hippel-Lindau (VHL) genes are the cause of VHL disease, which displays multiple benign and malignant tumors. The VHL gene has been shown to regulate angiogenic potential and glycolic metabolism via its E3 ubiquitin ligase function against the alpha subunit of hypoxia-inducible factor (HIF). However, many other HIF-independent functions of VHL have been identified and recent evidence indicates that the canonical function cannot fully explain the VHL mutant cell phenotypes. Many of these functions have not been verified in genetically tractable systems. Using an established follicular epithelial model in Drosophila, we show that the Drosophila VHL gene is involved in epithelial morphogenesis via stabilizing microtubule bundles and aPKC. Microtubule defects in VHL mutants lead to mislocalization of aPKC and subsequent loss of epithelial integrity. Destabilizing microtubules in ex vivo culture of wild-type egg chambers can also result in aPKC mislocalization and epithelial defects. Importantly, paclitaxel-induced stabilization of microtubules can rescue the aPKC localization phenotype in Drosophila VHL mutant follicle cells. The results establish a developmental function of the VHL gene that is relevant to its tumor-suppressor activity.</jats:p> |
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| author | Duchi, Serena, Fagnocchi, Luca, Cavaliere, Valeria, Hsouna, Anita, Gargiulo, Giuseppe, Hsu, Tien |
| author_facet | Duchi, Serena, Fagnocchi, Luca, Cavaliere, Valeria, Hsouna, Anita, Gargiulo, Giuseppe, Hsu, Tien, Duchi, Serena, Fagnocchi, Luca, Cavaliere, Valeria, Hsouna, Anita, Gargiulo, Giuseppe, Hsu, Tien |
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| description | <jats:p>Mutations in the human von Hippel-Lindau (VHL) genes are the cause of VHL disease, which displays multiple benign and malignant tumors. The VHL gene has been shown to regulate angiogenic potential and glycolic metabolism via its E3 ubiquitin ligase function against the alpha subunit of hypoxia-inducible factor (HIF). However, many other HIF-independent functions of VHL have been identified and recent evidence indicates that the canonical function cannot fully explain the VHL mutant cell phenotypes. Many of these functions have not been verified in genetically tractable systems. Using an established follicular epithelial model in Drosophila, we show that the Drosophila VHL gene is involved in epithelial morphogenesis via stabilizing microtubule bundles and aPKC. Microtubule defects in VHL mutants lead to mislocalization of aPKC and subsequent loss of epithelial integrity. Destabilizing microtubules in ex vivo culture of wild-type egg chambers can also result in aPKC mislocalization and epithelial defects. Importantly, paclitaxel-induced stabilization of microtubules can rescue the aPKC localization phenotype in Drosophila VHL mutant follicle cells. The results establish a developmental function of the VHL gene that is relevant to its tumor-suppressor activity.</jats:p> |
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| imprint | The Company of Biologists, 2010 |
| imprint_str_mv | The Company of Biologists, 2010 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-D161, DE-Zwi2, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14 |
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| spelling | Duchi, Serena Fagnocchi, Luca Cavaliere, Valeria Hsouna, Anita Gargiulo, Giuseppe Hsu, Tien 1477-9129 0950-1991 The Company of Biologists Developmental Biology Molecular Biology http://dx.doi.org/10.1242/dev.042804 <jats:p>Mutations in the human von Hippel-Lindau (VHL) genes are the cause of VHL disease, which displays multiple benign and malignant tumors. The VHL gene has been shown to regulate angiogenic potential and glycolic metabolism via its E3 ubiquitin ligase function against the alpha subunit of hypoxia-inducible factor (HIF). However, many other HIF-independent functions of VHL have been identified and recent evidence indicates that the canonical function cannot fully explain the VHL mutant cell phenotypes. Many of these functions have not been verified in genetically tractable systems. Using an established follicular epithelial model in Drosophila, we show that the Drosophila VHL gene is involved in epithelial morphogenesis via stabilizing microtubule bundles and aPKC. Microtubule defects in VHL mutants lead to mislocalization of aPKC and subsequent loss of epithelial integrity. Destabilizing microtubules in ex vivo culture of wild-type egg chambers can also result in aPKC mislocalization and epithelial defects. Importantly, paclitaxel-induced stabilization of microtubules can rescue the aPKC localization phenotype in Drosophila VHL mutant follicle cells. The results establish a developmental function of the VHL gene that is relevant to its tumor-suppressor activity.</jats:p> <i>Drosophila VHL</i> tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability Development |
| spellingShingle | Duchi, Serena, Fagnocchi, Luca, Cavaliere, Valeria, Hsouna, Anita, Gargiulo, Giuseppe, Hsu, Tien, Development, Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability, Developmental Biology, Molecular Biology |
| title | Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_full | Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_fullStr | Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_full_unstemmed | Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_short | Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| title_sort | <i>drosophila vhl</i> tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and apkc stability |
| title_unstemmed | Drosophila VHL tumor-suppressor gene regulates epithelial morphogenesis by promoting microtubule and aPKC stability |
| topic | Developmental Biology, Molecular Biology |
| url | http://dx.doi.org/10.1242/dev.042804 |