Cargando…

Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster

Polyamines are small organic cations that are essential for many biological processes such as cell proliferation and cell cycle progression. While the metabolism of polyamines has been well studied, the mechanisms by which polyamines are transported into and out of cells are poorly understood. Here,...

Descripción completa

Detalles Bibliográficos
Autores principales: Stump, Coryn L., Casero, Robert A., Phanstiel, Otto, DiAngelo, Justin R., Nowotarski, Shannon L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502369/
https://www.ncbi.nlm.nih.gov/pubmed/36135830
http://dx.doi.org/10.3390/medsci10030045
_version_ 1784795687960969216
author Stump, Coryn L.
Casero, Robert A.
Phanstiel, Otto
DiAngelo, Justin R.
Nowotarski, Shannon L.
author_facet Stump, Coryn L.
Casero, Robert A.
Phanstiel, Otto
DiAngelo, Justin R.
Nowotarski, Shannon L.
author_sort Stump, Coryn L.
collection PubMed
description Polyamines are small organic cations that are essential for many biological processes such as cell proliferation and cell cycle progression. While the metabolism of polyamines has been well studied, the mechanisms by which polyamines are transported into and out of cells are poorly understood. Here, we describe a novel role of Chmp1, a vesicular trafficking protein, in the transport of polyamines using a well-defined leg imaginal disc assay in Drosophila melanogaster larvae. We show that Chmp1 overexpression had no effect on leg development in Drosophila, but does attenuate the negative impact on leg development of Ant44, a cytotoxic drug known to enter cells through the polyamine transport system (PTS), suggesting that the overexpression of Chmp1 downregulated the PTS. Moreover, we showed that the addition of spermine did not rescue the leg development in Chmp1-overexpressing leg discs treated with difluoromethylornithine (DFMO), an inhibitor of polyamine metabolism, while putrescine and spermidine did, suggesting that there may be unique mechanisms of import for individual polyamines. Thus, our data provide novel insight into the underlying mechanisms that are involved in polyamine transport and highlight the utility of the Drosophila imaginal disc assay as a fast and easy way to study potential players involved in the PTS.
format Online
Article
Text
id pubmed-9502369
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-95023692022-09-24 Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster Stump, Coryn L. Casero, Robert A. Phanstiel, Otto DiAngelo, Justin R. Nowotarski, Shannon L. Med Sci (Basel) Brief Report Polyamines are small organic cations that are essential for many biological processes such as cell proliferation and cell cycle progression. While the metabolism of polyamines has been well studied, the mechanisms by which polyamines are transported into and out of cells are poorly understood. Here, we describe a novel role of Chmp1, a vesicular trafficking protein, in the transport of polyamines using a well-defined leg imaginal disc assay in Drosophila melanogaster larvae. We show that Chmp1 overexpression had no effect on leg development in Drosophila, but does attenuate the negative impact on leg development of Ant44, a cytotoxic drug known to enter cells through the polyamine transport system (PTS), suggesting that the overexpression of Chmp1 downregulated the PTS. Moreover, we showed that the addition of spermine did not rescue the leg development in Chmp1-overexpressing leg discs treated with difluoromethylornithine (DFMO), an inhibitor of polyamine metabolism, while putrescine and spermidine did, suggesting that there may be unique mechanisms of import for individual polyamines. Thus, our data provide novel insight into the underlying mechanisms that are involved in polyamine transport and highlight the utility of the Drosophila imaginal disc assay as a fast and easy way to study potential players involved in the PTS. MDPI 2022-08-25 /pmc/articles/PMC9502369/ /pubmed/36135830 http://dx.doi.org/10.3390/medsci10030045 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Stump, Coryn L.
Casero, Robert A.
Phanstiel, Otto
DiAngelo, Justin R.
Nowotarski, Shannon L.
Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster
title Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster
title_full Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster
title_fullStr Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster
title_full_unstemmed Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster
title_short Elucidating the Role of Chmp1 Overexpression in the Transport of Polyamines in Drosophila melanogaster
title_sort elucidating the role of chmp1 overexpression in the transport of polyamines in drosophila melanogaster
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9502369/
https://www.ncbi.nlm.nih.gov/pubmed/36135830
http://dx.doi.org/10.3390/medsci10030045
work_keys_str_mv AT stumpcorynl elucidatingtheroleofchmp1overexpressioninthetransportofpolyaminesindrosophilamelanogaster
AT caseroroberta elucidatingtheroleofchmp1overexpressioninthetransportofpolyaminesindrosophilamelanogaster
AT phanstielotto elucidatingtheroleofchmp1overexpressioninthetransportofpolyaminesindrosophilamelanogaster
AT diangelojustinr elucidatingtheroleofchmp1overexpressioninthetransportofpolyaminesindrosophilamelanogaster
AT nowotarskishannonl elucidatingtheroleofchmp1overexpressioninthetransportofpolyaminesindrosophilamelanogaster