Notch signaling during development requires the function of awd, the Drosophila homolog of human metastasis suppressor gene Nm23

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Title:	Notch signaling during development requires the function of awd, the Drosophila homolog of human metastasis suppressor gene Nm23
Authors:	徐沺;Ignesti, Marilena;Barraco, Marilena;Nallamothu, Gouthami;Woolworth, Julie A;Duchi, Serena;Gargiulo, Giuseppe;Cavaliere, Valeria;Hsu, Tien
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	Animals;Biomedical and Life Sciences;Cell Proliferation;Clone Cells;Cytoplasmic Vesicles;Drosophila;Drosophila melanogaster - genetics;Drosophila melanogaster - growth & development;Drosophila melanogaster - metabolism;Drosophila Proteins - metabolism;Endocytosis;Endosomes - metabolism;Female;Gene Expression Regulation, Developmental;Genes;Humans;Imaginal Discs - cytology;Kinases;Larva - growth & development;Larva - metabolism;Life Sciences;Medical research;Mutation - genetics;Neoplasm Metastasis;NM23 Nucleoside Diphosphate Kinases - genetics;NM23 Nucleoside Diphosphate Kinases - metabolism;Nucleoside-Diphosphate Kinase - metabolism;Ovarian Follicle - cytology;Ovarian Follicle - metabolism;Protein Transport;rab5 GTP-Binding Proteins - metabolism;Receptors, Notch - metabolism;Research Article;Sequence Homology, Amino Acid;Signal Transduction;Vascular endothelial growth factor;Wings, Animal - cytology;Wings, Animal - metabolism
Date:	2014-02-14
Issue Date:	2026-04-23 11:17:56 (UTC+8)
Publisher:	BioMed Central Ltd.;London: BioMed Central
Abstract:	摘要： Background The Drosophila abnormal wing discs ( awd ) belongs to a highly conserved family of genes implicated in metastasis suppression, metabolic homeostasis and epithelial morphogenesis. The cellular function of the mammalian members of this family, the Nm23 proteins, has not yet been clearly defined. Previous awd genetic analyses unraveled its endocytic role that is required for proper internalization of receptors controlling different signaling pathways. In this study, we analyzed the role of Awd in controlling Notch signaling during development. Results To study the awd gene function we used genetic mosaic approaches to obtain cells homozygous for a loss of function allele. In awd mutant follicle cells and wing disc cells, Notch accumulates in enlarged early endosomes, resulting in defective Notch signaling. Our results demonstrate that awd function is required before γ-secretase mediated cleavage since over-expression of the constitutively active form of the Notch receptor in awd mutant follicle cells allows rescue of the signaling. By using markers of different endosomal compartments we show that Notch receptor accumulates in early endosomes in awd mutant follicle cells. A trafficking assay in living wing discs also shows that Notch accumulates in early endosomes. Importantly, constitutively active Rab5 cannot rescue the awd phenotype, suggesting that awd is required for Rab5 function in early endosome maturation. Conclusions In this report we demonstrate that awd is essential for Notch signaling via its endocytic role. In addition, we identify the endocytic step at which Awd function is required for Notch signaling and we obtain evidence indicating that Awd is necessary for Rab5 function. These findings provide new insights into the developmental and pathophysiological function of this important gene family. 其他題名： BMC Biol 出版者： London: BioMed Central 出版日期： 2014-02-14 出處： BMC biology, 2014-02, Vol.12 (1), p.12-12, Article 12 資源來源： EBSCOhost Academic Search Premier 版權： Ignesti et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 版權： COPYRIGHT 2014 BioMed Central Ltd. 版權： 2014 Ignesti et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 版權： Copyright © 2014 Ignesti et al.; licensee BioMed Central Ltd. 2014 Ignesti et al.; licensee BioMed Central Ltd. 識別號： ISSN: 1741-7007 識別號： EISSN: 1741-7007 識別號： DOI: 10.1186/1741-7007-12-12 識別號： PMID: 24528630
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