Human cytomegalovirus pUL37x1 induces the release of endoplasmic reticulum calcium stores

Ronit Sharon-Friling, Joseph Goodhouse, Anamaris M. Colberg-Poley, Thomas Shenk

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

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 Ca2+ 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 Ca2+ chelating agent. The UL37x1-mediated release of Ca2+ 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.

Original languageEnglish (US)
Pages (from-to)19117-19122
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number50
DOIs
StatePublished - Dec 12 2006

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Actin cytoskeleton
  • Apoptosis
  • Cytopathic effect
  • Mitochondrial fission
  • Viral mitochondria-localized inhibitor of apoptosis

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