Enhanced Ca2+ leak from ER Ca2+ stores induced by hepatitis C NS5A protein

Lisbeth C. Robinson, Jonathan S. Marchant

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The hepatitis C non-structural protein 5A (NS5A) is a Zn2+-binding phosphoprotein essential for viral replication. Expression of NS5A perturbs intracellular Ca2+ levels by an undefined mechanism, activating transcription factors implicated in the chronic pathogenesis of hepatitis infections. Here, we demonstrate that regulated expression of NS5A enhanced the passive leak of Ca2+ from a subset of the endoplasmic reticulum (ER) Ca2+ stores. This action was not replicated by expression of the amphipathic NH2-membrane anchoring domain of NS5A alone, despite targeting to intracellular membranes. Depletion of the NS5A-targeted ER Ca2+ store was prevented under conditions of ample ATP supply suggesting compensatory Ca2+ ATPase activity, but observed under conditions of ATP insufficiency and in intact cells expressing NS5A.

Original languageEnglish (US)
Pages (from-to)593-599
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume368
Issue number3
DOIs
StatePublished - Apr 11 2008

Bibliographical note

Funding Information:
Supported by NIH (NS046783) and a NSF CAREER Fellowship (JSM, 0237946).

Keywords

  • Ca signaling
  • Endoplasmic reticulum

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