Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy

Macroautophagy/autophagy plays an important role in cellular copper clearance. The means by which the copper metabolism and autophagy pathways interact mechanistically is vastly unexplored. Dysfunctional ATP7B, a copper-transporting ATPase, is involved in the development of monogenic Wilson disease,...

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Autores principales:	Supansa Pantoom, Adam Pomorski, Katharina Huth, Christina Hund, Janine Petters, Artur Krężel, Andreas Hermann, Jan Lukas
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Wilson disease ATPase copper transporting beta autophagosome-lysosome fusion HepG2 LC3 interaction region Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/78e2c2325b5e4792b260a63e34cdd927
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spelling	oai:doaj.org-article:78e2c2325b5e4792b260a63e34cdd9272021-11-25T17:11:41ZDirect Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy10.3390/cells101131182073-4409https://doaj.org/article/78e2c2325b5e4792b260a63e34cdd9272021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3118https://doaj.org/toc/2073-4409Macroautophagy/autophagy plays an important role in cellular copper clearance. The means by which the copper metabolism and autophagy pathways interact mechanistically is vastly unexplored. Dysfunctional ATP7B, a copper-transporting ATPase, is involved in the development of monogenic Wilson disease, a disorder characterized by disturbed copper transport. Using in silico prediction, we found that ATP7B contains a number of potential binding sites for LC3, a central protein in the autophagy pathway, the so-called LC3 interaction regions (LIRs). The conserved LIR3, located at the C-terminal end of ATP7B, was found to directly interact with LC3B in vitro. Replacing the two conserved hydrophobic residues W1452 and L1455 of LIR3 significantly reduced interaction. Furthermore, autophagy was induced in normal human hepatocellular carcinoma cells (HepG2) leading to enhanced colocalization of ATP7B and LC3B on the autophagosome membranes. By contrast, HepG2 cells deficient of ATP7B (HepG2 ATP7B<sup>−/−</sup>) showed autophagy deficiency at elevated copper condition. This phenotype was complemented by heterologous ATP7B expression. These findings suggest a cooperative role of ATP7B and LC3B in autophagy-mediated copper clearance.Supansa PantoomAdam PomorskiKatharina HuthChristina HundJanine PettersArtur KrężelAndreas HermannJan LukasMDPI AGarticleWilson diseaseATPase copper transporting betaautophagosome-lysosome fusionHepG2LC3 interaction regionBiology (General)QH301-705.5ENCells, Vol 10, Iss 3118, p 3118 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Wilson disease ATPase copper transporting beta autophagosome-lysosome fusion HepG2 LC3 interaction region Biology (General) QH301-705.5
spellingShingle	Wilson disease ATPase copper transporting beta autophagosome-lysosome fusion HepG2 LC3 interaction region Biology (General) QH301-705.5 Supansa Pantoom Adam Pomorski Katharina Huth Christina Hund Janine Petters Artur Krężel Andreas Hermann Jan Lukas Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy
description	Macroautophagy/autophagy plays an important role in cellular copper clearance. The means by which the copper metabolism and autophagy pathways interact mechanistically is vastly unexplored. Dysfunctional ATP7B, a copper-transporting ATPase, is involved in the development of monogenic Wilson disease, a disorder characterized by disturbed copper transport. Using in silico prediction, we found that ATP7B contains a number of potential binding sites for LC3, a central protein in the autophagy pathway, the so-called LC3 interaction regions (LIRs). The conserved LIR3, located at the C-terminal end of ATP7B, was found to directly interact with LC3B in vitro. Replacing the two conserved hydrophobic residues W1452 and L1455 of LIR3 significantly reduced interaction. Furthermore, autophagy was induced in normal human hepatocellular carcinoma cells (HepG2) leading to enhanced colocalization of ATP7B and LC3B on the autophagosome membranes. By contrast, HepG2 cells deficient of ATP7B (HepG2 ATP7B<sup>−/−</sup>) showed autophagy deficiency at elevated copper condition. This phenotype was complemented by heterologous ATP7B expression. These findings suggest a cooperative role of ATP7B and LC3B in autophagy-mediated copper clearance.
format	article
author	Supansa Pantoom Adam Pomorski Katharina Huth Christina Hund Janine Petters Artur Krężel Andreas Hermann Jan Lukas
author_facet	Supansa Pantoom Adam Pomorski Katharina Huth Christina Hund Janine Petters Artur Krężel Andreas Hermann Jan Lukas
author_sort	Supansa Pantoom
title	Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy
title_short	Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy
title_full	Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy
title_fullStr	Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy
title_full_unstemmed	Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy
title_sort	direct interaction of atp7b and lc3b proteins suggests a cooperative role of copper transportation and autophagy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/78e2c2325b5e4792b260a63e34cdd927
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Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy

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