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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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Autores principales: Mezzofanti, Elisa, Ignesti, Marilena, Hsu, Tien, Gargiulo, Giuseppe, Cavaliere, Valeria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687847/
https://www.ncbi.nlm.nih.gov/pubmed/31427986
http://dx.doi.org/10.3389/fphys.2019.00983
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author Mezzofanti, Elisa
Ignesti, Marilena
Hsu, Tien
Gargiulo, Giuseppe
Cavaliere, Valeria
author_facet Mezzofanti, Elisa
Ignesti, Marilena
Hsu, Tien
Gargiulo, Giuseppe
Cavaliere, Valeria
author_sort Mezzofanti, Elisa
collection PubMed
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.
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spelling pubmed-66878472019-08-19 Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2 Mezzofanti, Elisa Ignesti, Marilena Hsu, Tien Gargiulo, Giuseppe Cavaliere, Valeria Front Physiol Physiology 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. Frontiers Media S.A. 2019-08-02 /pmc/articles/PMC6687847/ /pubmed/31427986 http://dx.doi.org/10.3389/fphys.2019.00983 Text en Copyright © 2019 Mezzofanti, Ignesti, Hsu, Gargiulo and Cavaliere. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Mezzofanti, Elisa
Ignesti, Marilena
Hsu, Tien
Gargiulo, Giuseppe
Cavaliere, Valeria
Vps28 Is Involved in the Intracellular Trafficking of Awd, the Drosophila Homolog of NME1/2
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 Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687847/
https://www.ncbi.nlm.nih.gov/pubmed/31427986
http://dx.doi.org/10.3389/fphys.2019.00983
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