Medical College of Wisconsin
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Enhanced Ca2+ leak from ER Ca2+ stores induced by hepatitis C NS5A protein. Biochem Biophys Res Commun 2008 Apr 11;368(3):593-9

Date

02/09/2008

Pubmed ID

18258181

Pubmed Central ID

PMC2292798

DOI

10.1016/j.bbrc.2008.01.127

Scopus ID

2-s2.0-39749118497   19 Citations

Abstract

The hepatitis C non-structural protein 5A (NS5A) is a Zn(2+)-binding phosphoprotein essential for viral replication. Expression of NS5A perturbs intracellular Ca(2+) 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(2+) from a subset of the endoplasmic reticulum (ER) Ca(2+) stores. This action was not replicated by expression of the amphipathic NH(2)-membrane anchoring domain of NS5A alone, despite targeting to intracellular membranes. Depletion of the NS5A-targeted ER Ca(2+) store was prevented under conditions of ample ATP supply suggesting compensatory Ca(2+) ATPase activity, but observed under conditions of ATP insufficiency and in intact cells expressing NS5A.

Author List

Robinson LC, Marchant JS

Author

Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Cell Line
Cell Membrane
Endoplasmic Reticulum
Kidney
Viral Nonstructural Proteins
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a