Exosomal secretion of truncated cytosolic lysyl-tRNA synthetase induces inflammation during cell starvation
Authors:Sang Bum Kim1,2, Seongmin Cho1, 2 and Sunghoon Kim1,2
1 Medicinal Bioconvergence Research Center, Seoul National University, Suwon, South Korea.
2 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea.
Keywords:
lysyl-tRNA synthetase, exosome, syntenin, caspase-8, inflammation.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no competing financial interests.
Please cite this article as:
Sang Bum Kim, Seongmin Cho and Sunghoon Kim (2018). Exosomal secretion of truncated cytosolic lysyl-tRNA synthetase induces inflammation during cell starvation. Cell Stress 2(5): 119-121. doi: 10.15698/cst2018.05.137
© 2018 Kim et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Previous work by Kim, et al. (2017) unveiled that lysyl-tRNA synthetase (KRS) is secreted through a mechanism involving syntenin-containing exosomes. They described how KRS, commonly known as part of the translational machinery in the cytoplasm, is secreted into the extracellular space where it induces inflammation. First, KRS secretion is triggered by starvation conditions. The increase in caspase-8 levels during starvation is responsible for proteolysis and generation of the N-terminal truncated form of KRS, and this event is required for KRS dissociation from the multi-synthetase complex (MSC). N-terminal cleavage of KRS eventually leads to a conformational change that allows its interaction with the C-terminal PDZ binding motif of syntenin and subsequent exosome biogenesis. The KRS-syntenin complex translocates to multivesicular bodies (MVBs) that originate from endosomes involved with intraluminal vesicle (ILVs). MVBs are transporters for the secretion of cellular contents into the extracellular space. Syntenin localizes intraluminal vesicles within endosomal membranes. The KRS-syntenin complex transfers on to intraluminal vesicles in MVBs. MVBs are translocated to the plasma membrane for ILV secretion mediated by Rab family proteins. Once KRS exosomes are secreted, their membranes are eventually ruptured by proteases and KRS is released from the exosomes where it can act as an inflammatory cytokine in the extracellular space. Secreted KRS triggers macrophage/neutrophil migration and induces inflammation.