PMID- 23442576 OWN - NLM STAT- MEDLINE DCOM- 20131122 LR - 20211021 IS - 1554-8635 (Electronic) IS - 1554-8627 (Print) IS - 1554-8627 (Linking) VI - 9 IP - 5 DP - 2013 May TI - Viroporin-mediated calcium-activated autophagy. PG - 797-8 LID - 10.4161/auto.23959 [doi] AB - Autophagy is a cellular response activated by many pathogens, but the mechanism of activation is largely unknown. Recently we showed for the first time that rotavirus initiates the autophagy pathway through a calcium-mediated mechanism. Expression of the rotavirus-encoded NSP4, a pore-forming protein (viroporin), elicits the release of endoplasmic reticulum (ER) lumenal calcium into the cytoplasm of the infected cell. The increased cytoplasmic calcium activates a calcium signaling pathway involving calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and 5' adenosine monophosphate-activated protein kinase (AMPK) to trigger autophagy. Rotavirus further manipulates autophagy membrane trafficking to transport viral ER-associated proteins to viroplasms, sites of viral genome replication and immature particle assembly. Transport of viral proteins to viroplasms is required for assembly of infectious virus. Thus, NSP4, a multifunctional viral protein known to regulate infectious particle assembly, also modulates membrane trafficking by orchestrating the activation of autophagy to benefit viral replication. FAU - Crawford, Sue E AU - Crawford SE AD - Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA. FAU - Estes, Mary K AU - Estes MK LA - eng GR - P30 DK056338/DK/NIDDK NIH HHS/United States GR - R01 AI080656/AI/NIAID NIH HHS/United States PT - Journal Article DEP - 20130226 PL - United States TA - Autophagy JT - Autophagy JID - 101265188 RN - 0 (Glycoproteins) RN - 0 (NS28 protein, rotavirus) RN - 0 (Toxins, Biological) RN - 0 (Viral Nonstructural Proteins) RN - SY7Q814VUP (Calcium) SB - IM CON - Crawford SE, Hyser JM, Utama B, Estes MK. Autophagy hijacked through viroporin-activated calcium/calmodulin-dependent kinase kinase-beta signaling is required for rotavirus replication. Proc Natl Acad Sci U S A. 2012;109:E3405-13. doi: 10.1073/pnas.1216539109. MH - Animals MH - Autophagy/drug effects MH - Calcium/*pharmacology MH - Endoplasmic Reticulum/drug effects/metabolism MH - Glycoproteins/*metabolism MH - Humans MH - Models, Biological MH - Rotavirus/drug effects/physiology MH - Signal Transduction/*drug effects MH - Toxins, Biological/*metabolism MH - Viral Nonstructural Proteins/*metabolism MH - Virus Assembly/drug effects PMC - PMC3669193 OTO - NOTNLM OT - autophagy OT - calcium OT - kinase OT - stress OT - virus EDAT- 2013/02/28 06:00 MHDA- 2013/12/16 06:00 PMCR- 2014/05/01 CRDT- 2013/02/28 06:00 PHST- 2013/02/28 06:00 [entrez] PHST- 2013/02/28 06:00 [pubmed] PHST- 2013/12/16 06:00 [medline] PHST- 2014/05/01 00:00 [pmc-release] AID - 23959 [pii] AID - 2013AUTO0104 [pii] AID - 10.4161/auto.23959 [doi] PST - ppublish SO - Autophagy. 2013 May;9(5):797-8. doi: 10.4161/auto.23959. Epub 2013 Feb 26.