ATP13A3 is a major component of the enigmatic mammalian polyamine transport system.
ATP13A3
P-type ATPase
P5B-ATPase
polyamine
polyamine transport system
putrescine
transporter
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
15
04
2020
revised:
27
11
2020
accepted:
11
12
2020
pubmed:
15
12
2020
medline:
19
8
2021
entrez:
14
12
2020
Statut:
ppublish
Résumé
Polyamines, such as putrescine, spermidine, and spermine, are physiologically important polycations, but the transporters responsible for their uptake in mammalian cells remain poorly characterized. Here, we reveal a new component of the mammalian polyamine transport system using CHO-MG cells, a widely used model to study alternative polyamine uptake routes and characterize polyamine transport inhibitors for therapy. CHO-MG cells present polyamine uptake deficiency and resistance to a toxic polyamine biosynthesis inhibitor methylglyoxal bis-(guanylhydrazone) (MGBG), but the molecular defects responsible for these cellular characteristics remain unknown. By genome sequencing of CHO-MG cells, we identified mutations in an unexplored gene, ATP13A3, and found disturbed mRNA and protein expression. ATP13A3 encodes for an orphan P5B-ATPase (ATP13A3), a P-type transport ATPase that represents a candidate polyamine transporter. Interestingly, ATP13A3 complemented the putrescine transport deficiency and MGBG resistance of CHO-MG cells, whereas its knockdown in WT cells induced a CHO-MG phenotype demonstrated as a decrease in putrescine uptake and MGBG sensitivity. Taken together, our findings identify ATP13A3, which has been previously genetically linked with pulmonary arterial hypertension, as a major component of the mammalian polyamine transport system that confers sensitivity to MGBG.
Identifiants
pubmed: 33310703
pii: S0021-9258(20)00178-7
doi: 10.1074/jbc.RA120.013908
pmc: PMC7948421
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Membrane Transport Proteins
0
Polyamines
0
Adenosine Triphosphatases
EC 3.6.1.-
Mitoguazone
OD5Q0L447W
Putrescine
V10TVZ52E4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100182Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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