- Meeting abstract
- Open Access
Roles of 8-nitro-cGMP in autophagy regulation
© Arimoto 2015
- Published: 2 September 2015
- Reactive Oxygen Species
- Nitric Oxide
- Mammalian Cell Line
- Polyubiquitin Chain
- Downstream Mediator
A downstream mediator of nitric oxide signaling, 8-nitroguanosine 3?,5?-cyclic monophosphate (8-nitro-cGMP), has been recently identified in various mammalian cell lines [1, 2]. This nitrated version of cGMP modifies Cys residues of proteins (protein S-guanylation) to modulate their functions. In this study, we found that endogenous 8-nitro-cGMP promotes autophagic exclusion of invading group A Streptococci (GAS) from murine macrophages . Interestingly, cytosolic GAS were partly modified by the S-guanylation at their surface, and the S-guanylation level was significantly higher with the autophagosome-encapsulated GAS than the cytosolic counterpart. This finding suggests a possible role of S-guanylation as a tag to recruit bacteria for autophagic degradation. Further analysis revealed that S-guanylation-positive bacteria were selectively modified by Lys63-linked polyubiquitin chains, which is a known molecular determinant for selective transport to autophagosomes via autophagy receptor binding. In accordance with this finding, downregulation of S-guanylation suppressed GAS ubiquitination and retarded the clearance of intracellular GAS.
The results of our study suggested that 8-nitro-cGMP is an endogenous autophagy enhancer that defines targets for sequestration in autophagosomes by recruiting ubiquitin chains.
- Sawa T, Zaki MH, Okamoto T, Akuta T, Tokutomi Y, Mitsuyama SK, Ihara H, Kobayashi A, Yamamoto M, Fujii S, Arimoto H, Akaike T: Protein S-guanylation by the biological signal 8-nitroguanosine 3',5'-cyclic monophosphate. Nature Chemical Biology. 2007, 3: 727-735. 10.1038/nchembio.2007.33.View ArticlePubMedGoogle Scholar
- Saito Y, Sawa T, Yoshitake J, Ito C, Fujii S, Akaike T, Arimoto H: Nitric oxide promotes recycling of 8-nitro-cGMP, a cytoprotective mediator, into intact cGMP in cell. Molecular BioSystems. 2012, 8: 2909-2915. 10.1039/c2mb25189b.View ArticlePubMedGoogle Scholar
- Ito C, Saito Y, Nozawa T, Fujii S, Sawa T, Inoue H, Matsunaga T, Khan S, Akashi S, Hashimoto R, Aikawa C, Takahashi E, Sagara H, Komatsu M, Tanaka K, Akaike T, Nakagawa I, Arimoto H: Endogenous nitrated nucleotide is a key mediator of autophagy and innate defense against bacteria. Molecular Cell. 2013, 52: 794-804. 10.1016/j.molcel.2013.10.024.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.