Enhanced Ca super(2) super(+) leak from ER Ca super(2) super(+) stores induced by hepatitis C NS5A protein

The hepatitis C non-structural protein 5A (NS5A) is a Zn super(2) super(+)-binding phosphoprotein essential for viral replication. Expression of NS5A perturbs intracellular Ca super(2) super(+) levels by an undefined mechanism, activating transcription factors implicated in the chronic pathogenesis...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-04, Vol.368 (3), p.593-599
Main Authors: Robinson, L C, Marchant, J S
Format: Article
Language:English
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Summary:The hepatitis C non-structural protein 5A (NS5A) is a Zn super(2) super(+)-binding phosphoprotein essential for viral replication. Expression of NS5A perturbs intracellular Ca super(2) super(+) 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 Ca super(2) super(+) from a subset of the endoplasmic reticulum (ER) Ca super(2) super(+) stores. This action was not replicated by expression of the amphipathic NH sub(2)-membrane anchoring domain of NS5A alone, despite targeting to intracellular membranes. Depletion of the NS5A-targeted ER Ca super(2) super(+) store was prevented under conditions of ample ATP supply suggesting compensatory Ca super(2) super(+) ATPase activity, but observed under conditions of ATP insufficiency and in intact cells expressing NS5A.
ISSN:0006-291X
DOI:10.1016/j.bbrc.2008.01.127