TY  - JOUR
AU  - Pantoom, Supansa
AU  - Pomorski, Adam
AU  - Huth, Katharina
AU  - Hund, Christina
AU  - Petters, Janine
AU  - Krężel, Artur
AU  - Hermann, Andreas
AU  - Lukas, Jan
TI  - Direct Interaction of ATP7B and LC3B Proteins Suggests a Cooperative Role of Copper Transportation and Autophagy.
JO  - Cells
VL  - 10
IS  - 11
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DZNE-2022-00268
SP  - 3118
PY  - 2021
N1  - (CC BY)
AB  - 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-/-) 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.
KW  - Amino Acid Sequence
KW  - Biological Transport: drug effects
KW  - Copper: metabolism
KW  - Copper: pharmacology
KW  - Copper-Transporting ATPases: chemistry
KW  - Copper-Transporting ATPases: metabolism
KW  - Hep G2 Cells
KW  - Humans
KW  - Microtubule-Associated Proteins: metabolism
KW  - Protein Binding: drug effects
KW  - Protein Transport: drug effects
KW  - ATPase copper transporting beta (Other)
KW  - HepG2 (Other)
KW  - LC3 interaction region (Other)
KW  - Wilson disease (Other)
KW  - autophagosome-lysosome fusion (Other)
KW  - MAP1LC3B protein, human (NLM Chemicals)
KW  - Microtubule-Associated Proteins (NLM Chemicals)
KW  - Copper (NLM Chemicals)
KW  - ATP7B protein, human (NLM Chemicals)
KW  - Copper-Transporting ATPases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:34831341
C2  - pmc:PMC8625360
DO  - DOI:10.3390/cells10113118
UR  - https://pub.dzne.de/record/163508
ER  -