A Glimpse into the Regulation of the Wilson Disease Protein, ATP7B, Sheds Light on the Complexity of Mammalian Apical Trafficking Pathways

Overview

Journal Metallomics

Publisher Oxford University Press

Date 2018 Feb 24

PMID 29473088

Citations 6

Authors

Arnab Gupta

Santanu Das

Kunal Ray

Affiliations

Soon will be listed here.

Abstract

Wilson disease (WD), a Mendelian disorder of copper metabolism caused by mutations in the ATP7B gene, manifests a large spectrum of phenotypic variability. This phenomenon of extensive symptom variation is not frequently associated with a monogenic disorder. We hypothesize that the phenotypic variability in WD is primarily driven by the variations in interacting proteins that regulate the ATP7B function and localization in the cell. Based on existing literature, we delineated a potential molecular mechanism for ATP7B mediated copper transport in the milieu of its interactome, its dysfunction in WD and the resulting variability in the phenotypic manifestation. Understanding the copper-induced apical trafficking of ATP7B also significantly contributes to the appreciation of the complexities of the ligand-induced transport pathway. We believe that this holistic view of WD will pave the way for a better opportunity for rational drug design and therapeutics.

Citing Articles

Regulation of the apico-basolateral trafficking polarity of the homologous copper-ATPases ATP7A and ATP7B.

Ruturaj , Mishra M, Saha S, Maji S, Rodriguez-Boulan E, Schreiner R J Cell Sci. 2023; 137(5).

PMID: 38032054 PMC: 10729821. DOI: 10.1242/jcs.261258.

Wilson disease-causing mutations in the carboxyl terminus of ATP7B regulates its localization and Golgi exit selectively in the unpolarized cells.

Chakraborty K, Das S, Pal A, Maji S, Rai B, Gupta A Metallomics. 2023; 15(9).

PMID: 37660282 PMC: 10506129. DOI: 10.1093/mtomcs/mfad051.

Genetic studies discover novel coding and non-coding mutations in patients with Wilson's disease in China.

Huang C, Fang M, Xiao X, Gao Z, Wang Y, Gao C J Clin Lab Anal. 2022; 36(6):e24459.

PMID: 35470480 PMC: 9169201. DOI: 10.1002/jcla.24459.

Retromer retrieves the Wilson disease protein ATP7B from endolysosomes in a copper-dependent manner.

Das S, Maji S, Ruturaj , Bhattacharya I, Saha T, Naskar N J Cell Sci. 2020; 133(24).

PMID: 33268466 PMC: 7611186. DOI: 10.1242/jcs.246819.

ATP7B Binds Ruthenium(II) -Cymene Half-Sandwich Complexes: Role of Steric Hindrance and Ru-I Coordination in Rescuing the Sequestration.

Purkait K, Ruturaj , Mukherjee A, Gupta A Inorg Chem. 2019; 58(22):15659-15670.

PMID: 31657924 PMC: 7165018. DOI: 10.1021/acs.inorgchem.9b02780.

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