Tryptophan-dependent and -independent secretions of tryptophanyl- tRNA synthetase mediate innate inflammatory responses

Tram Thuy Thuy Nguyen, Yun Hui Choi, Won Kyu Lee, Yeounjung Ji, Eunho Chun, Yi Hyo Kim, Joo Eun Lee, Hyun Suk Jung, Ji Hun Suh, Sunghoon Kim, Mirim Jin

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

While cytoplasmic tryptophanyl-tRNA synthetase (WARS1) ligates tryptophan (Trp) to its cognate tRNAs for protein synthesis, it also plays a role as an innate immune activator in extracellular space. However, its secretion mechanism remains elusive. Here, we report that in response to stimuli, WARS1 can be secreted via two distinct pathways: via Trp-dependent secretion of naked protein and via Trp-independent plasma-membrane-derived vesicles (PMVs). In the direct pathway, Trp binding to WARS1 induces a “closed” conformation, generating a hydrophobic surface and basic pocket. The Trp-bound WARS1 then binds stable phosphatidylinositol (4,5)-biphosphate and inner plasma membrane leaflet, passing across the membrane. In the PMV-mediated secretion, WARS1 recruits calpain 2, which is activated by calcium. WARS1 released from PMVs induces inflammatory responses in vivo. These results provide insights into the secretion mechanisms of WARS1 and improve our understanding of how WARS1 is involved in the control of local and systemic inflammation upon infection.

Original languageEnglish
Article number111905
JournalCell Reports
Volume42
Issue number1
DOIs
Publication statusPublished - 2023 Jan 31

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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