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
02/09/2008Pubmed ID
18258181Pubmed Central ID
PMC2292798DOI
10.1016/j.bbrc.2008.01.127Scopus ID
2-s2.0-39749118497 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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 JSAuthor
Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCalcium
Cell Line
Cell Membrane
Endoplasmic Reticulum
Kidney
Viral Nonstructural Proteins
