Human cytomegalovirus pUL37x1 induces the release of endoplasmic reticulum calcium stores.
The human CMV UL37x1-encoded protein, also known as the viral mitochondria-localized inhibitor of apoptosis, traffics to the endoplasmic reticulum and mitochondria of infected cells. It induces the fragmentation of mitochondria and blocks apoptosis. We demonstrate that UL37x1 protein mobilizes Ca(2+) from the endoplasmic reticulum into the cytosol. This release is accompanied by cell rounding, cell swelling, and reorganization of the actin cytoskeleton, and these morphological changes can be substantially blocked by a Ca(2+) chelating agent. The UL37x1-mediated release of Ca(2+) from the endoplasmic reticulum likely has multiple consequences, including induction of the unfolded protein response, modulation of mitochondrial function, induction of mitochondrial fission, and protection against apoptotic stimuli.
Sharon-Friling
Ronit
R
Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA.
Goodhouse
Joseph
J
Colberg-Poley
Anamaris M
AM
Shenk
Thomas
T
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D017874:Immediate-Early Proteins; C420323:UL37 protein, Human herpesvirus 5; D014764:Viral Proteins; D002118:Calcium