Myosin Vb mediates Cu+ export in polarized hepatocytes

Arnab Gupta, Michael J. Schell, Ashima Bhattacharjee, Svetlana Lutsenko, Ann Louise Hubbard

Research output: Contribution to journalArticle

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 loss of function of myosin Vb.

Original languageEnglish (US)
Pages (from-to)1179-1189
Number of pages11
JournalJournal of Cell Science
Volume129
Issue number6
DOIs
StatePublished - 2016

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Myosins
Hepatocytes
Tubulin
Actins
Liver

Keywords

  • Apical
  • ATP7B
  • Cu
  • Endosome
  • Hepatocyte
  • Myosin
  • Trafficking

ASJC Scopus subject areas

  • Cell Biology

Cite this

Myosin Vb mediates Cu+ export in polarized hepatocytes. / Gupta, Arnab; Schell, Michael J.; Bhattacharjee, Ashima; Lutsenko, Svetlana; Hubbard, Ann Louise.

In: Journal of Cell Science, Vol. 129, No. 6, 2016, p. 1179-1189.

Research output: Contribution to journalArticle

Gupta, Arnab ; Schell, Michael J. ; Bhattacharjee, Ashima ; Lutsenko, Svetlana ; Hubbard, Ann Louise. / Myosin Vb mediates Cu+ export in polarized hepatocytes. In: Journal of Cell Science. 2016 ; Vol. 129, No. 6. pp. 1179-1189.
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