TY - JOUR
T1 - Enhanced Ca2+ leak from ER Ca2+ stores induced by hepatitis C NS5A protein
AU - Robinson, Lisbeth C.
AU - Marchant, Jonathan S.
N1 - Funding Information:
Supported by NIH (NS046783) and a NSF CAREER Fellowship (JSM, 0237946).
PY - 2008/4/11
Y1 - 2008/4/11
N2 - 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.
AB - 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.
KW - Ca signaling
KW - Endoplasmic reticulum
UR - http://www.scopus.com/inward/record.url?scp=39749118497&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=39749118497&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.01.127
DO - 10.1016/j.bbrc.2008.01.127
M3 - Article
C2 - 18258181
AN - SCOPUS:39749118497
SN - 0006-291X
VL - 368
SP - 593
EP - 599
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -