Journal
NATURE IMMUNOLOGY
Volume 14, Issue 5, Pages 454-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2550
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science
- Japan Society for the Promotion of Science Funding Program for World-Leading Innovative R&D on Science and Technology 'FIRST Program'
- Japan Science and Technology Agency Core Research for Evolutional Science and Technology
- Grants-in-Aid for Scientific Research [20002008, 13J06945] Funding Source: KAKEN
Ask authors/readers for more resources
NLRP3 forms an inflammasome with its adaptor ASC, and its excessive activation can cause inflammatory diseases. However, little is known about the mechanisms that control assembly of the inflammasome complex. Here we show that microtubules mediated assembly of the NLRP3 inflammasome. Inducers of the NLRP3 inflammasome caused aberrant mitochondrial homeostasis to diminish the concentration of the coenzyme NAD(+), which in turn inactivated the NAD(+)-dependent alpha-tubulin deacetylase sirtuin 2; this resulted in the accumulation of acetylated alpha-tubulin. Acetylated alpha-tubulin mediated the dynein-dependent transport of mitochondria and subsequent apposition of ASC on mitochondria to NLRP3 on the endoplasmic reticulum. Therefore, in addition to direct activation of NLRP3, the creation of optimal sites for signal transduction by microtubules is required for activation of the entire NLRP3 inflammasome.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available