Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2
The Awd (abnormal wing discs) gene is the Drosophila homolog of human NME1 and NME2 metastasis suppressor genes. These genes play a key role in tumor progression. Extensive studies revealed that intracellular NME1/2 protein levels could be related to either favorable or poor prognosis depending on t...
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| Format: | Article |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2019.00983/full |
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| author | Elisa Mezzofanti Marilena Ignesti Tien Hsu Tien Hsu Giuseppe Gargiulo Valeria Cavaliere |
| author_facet | Elisa Mezzofanti Marilena Ignesti Tien Hsu Tien Hsu Giuseppe Gargiulo Valeria Cavaliere |
| author_sort | Elisa Mezzofanti |
| collection | DOAJ |
| description | The Awd (abnormal wing discs) gene is the Drosophila homolog of human NME1 and NME2 metastasis suppressor genes. These genes play a key role in tumor progression. Extensive studies revealed that intracellular NME1/2 protein levels could be related to either favorable or poor prognosis depending on tissue context. More recently, extracellular activities of NME1/2 proteins have also been reported, including a tumor- promoting function. We used Drosophila as a genetic model to investigate the mechanism controlling intra- and extracellular levels of NME1/2. We examined the role of several components of the ESCRT (endosomal sorting complex required for transport) complex in controlling Awd trafficking. We show that the Vps28 component of the ESCRT−I complex is required for maintenance of normal intracellular level of Awd in larval adipocytes. We already showed that blocking of Shibire (Shi)/Dynamin function strongly- lowers Awd intracellular level. To further investigate this down regulative effect, we analyzed the distribution of endosomal markers in wild type and Shi-defective adipocytes. Our results suggest that Awd does not enter CD63-positive endosomes. Interestingly, we found that in fat body cells, Awd partly- colocalizes with the ESCRT accessory component ALiX, the ALG-2 (apoptosis-linked gene 2)-interacting protein X. Moreover, we show that the intracellular levels of both proteins are downregulated by blocking the function of the Dynamin encoded by the shibire gene. |
| first_indexed | 2024-12-23T14:06:53Z |
| format | Article |
| id | doaj.art-578a1c826ebc4bf49ca162c2c39ef9db |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-23T14:06:53Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-578a1c826ebc4bf49ca162c2c39ef9db2022-12-21T17:44:10ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-08-011010.3389/fphys.2019.00983443932Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2Elisa Mezzofanti0Marilena Ignesti1Tien Hsu2Tien Hsu3Giuseppe Gargiulo4Valeria Cavaliere5Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum – Università di Bologna, Bologna, ItalyDipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum – Università di Bologna, Bologna, ItalyDepartment of Biomedical Sciences and Engineering, National Central University, Zhongli, TaiwanCenter for Chronic Disease Management and Research, National Central University, Zhongli, TaiwanDipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum – Università di Bologna, Bologna, ItalyDipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum – Università di Bologna, Bologna, ItalyThe Awd (abnormal wing discs) gene is the Drosophila homolog of human NME1 and NME2 metastasis suppressor genes. These genes play a key role in tumor progression. Extensive studies revealed that intracellular NME1/2 protein levels could be related to either favorable or poor prognosis depending on tissue context. More recently, extracellular activities of NME1/2 proteins have also been reported, including a tumor- promoting function. We used Drosophila as a genetic model to investigate the mechanism controlling intra- and extracellular levels of NME1/2. We examined the role of several components of the ESCRT (endosomal sorting complex required for transport) complex in controlling Awd trafficking. We show that the Vps28 component of the ESCRT−I complex is required for maintenance of normal intracellular level of Awd in larval adipocytes. We already showed that blocking of Shibire (Shi)/Dynamin function strongly- lowers Awd intracellular level. To further investigate this down regulative effect, we analyzed the distribution of endosomal markers in wild type and Shi-defective adipocytes. Our results suggest that Awd does not enter CD63-positive endosomes. Interestingly, we found that in fat body cells, Awd partly- colocalizes with the ESCRT accessory component ALiX, the ALG-2 (apoptosis-linked gene 2)-interacting protein X. Moreover, we show that the intracellular levels of both proteins are downregulated by blocking the function of the Dynamin encoded by the shibire gene.https://www.frontiersin.org/article/10.3389/fphys.2019.00983/fullAwd/NMEmetastasis suppressor genesintracellular traffickingESCRT machineryVps28ALiX |
| spellingShingle | Elisa Mezzofanti Marilena Ignesti Tien Hsu Tien Hsu Giuseppe Gargiulo Valeria Cavaliere Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2 Frontiers in Physiology Awd/NME metastasis suppressor genes intracellular trafficking ESCRT machinery Vps28 ALiX |
| title | Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2 |
| title_full | Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2 |
| title_fullStr | Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2 |
| title_full_unstemmed | Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2 |
| title_short | Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2 |
| title_sort | vps28 is involved in the intracellular trafficking of awd the drosophila homolog of nme1 2 |
| topic | Awd/NME metastasis suppressor genes intracellular trafficking ESCRT machinery Vps28 ALiX |
| url | https://www.frontiersin.org/article/10.3389/fphys.2019.00983/full |
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