Myosin Vb mediates Cu+ export in polarized hepatocytes

Journal of Cell Science
Arnab GuptaAnn L Hubbard

Abstract

The cellular machinery responsible for Cu(+)-stimulated delivery of the Wilson-disease-associated protein ATP7B to the apical domain of hepatocytes is poorly understood. We demonstrate that myosin Vb regulates the Cu(+)-stimulated delivery of ATP7B to the apical domain of polarized hepatic cells, and that disruption of the ATP7B-myosin Vb interaction reduces the apical surface expression of ATP7B. Overexpression of the myosin Vb tail, which competes for binding of subapical cargos to myosin Vb bound to subapical actin, disrupted the surface expression of ATP7B, leading to reduced cellular Cu(+) export. The myosin-Vb-dependent targeting step occurred in parallel with hepatocyte-like polarity. If the myosin Vb tail was expressed acutely in cells just prior to the establishment of polarity, it appeared as part of an intracellular apical compartment, centered on γ-tubulin. ATP7B became selectively arrested in this compartment at high [Cu(+)] in the presence of myosin Vb tail, suggesting that these compartments are precursors of donor-acceptor transfer stations for apically targeted cargos of myosin Vb. Our data suggest that reduced hepatic Cu(+) clearance in idiopathic non-Wilsonian types of disease might be associated with the los...Continue Reading

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Citations

Jul 8, 2017·Metallomics : Integrated Biometal Science·Helena ÖhrvikNina Horn
Aug 14, 2019·FEBS Letters·Roman S Polishchuk, Elena V Polishchuk
Aug 2, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dong FuKim L R Brouwer
Nov 22, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Arend W OvereemSven C D van Ijzendoorn
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Takahiro ShimizuHideki Sakai
Nov 5, 2021·Journal of Cell Science·Svetlana Lutsenko

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