Essential role for GABARAP autophagy proteins in interferon-inducible GTPase-mediated host defense

Miwa Sasai, Naoya Sakaguchi, Ji Su Ma, Shuhei Nakamura, Tsuyoshi Kawabata, Hironori Bando, Youngae Lee, Tatsuya Saitoh, Shizuo Akira, Akiko Iwasaki, Daron M. Standley, Tamotsu Yoshimori, Masahiro Yamamoto

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

Mammalian autophagy-related 8 (Atg8) homologs consist of LC3 proteins and GABARAPs, all of which are known to be involved in canonical autophagy. In contrast, the roles of Atg8 homologs in noncanonical autophagic processes are not fully understood. Here we show a unique role of GABARAPs, in particular gamma-aminobutyric acid (GABA)-A-receptor-associated protein-like 2 (Gabarapl2; also known as Gate-16), in interferon-3 (IFN-3)-mediated antimicrobial responses. Cells that lacked GABARAPs but not LC3 proteins and mice that lacked Gate-16 alone were defective in the IFN-3-induced clearance of vacuolar pathogens such as Toxoplasma. Gate-16 but not LC3b specifically associated with the small GTPase ADP-ribosylation factor 1 (Arf1) to mediate uniform distribution of interferon-inducible GTPases. The lack of GABARAPs reduced Arf1 activation, which led to formation of interferon-inducible GTPase-containing aggregates and hampered recruitment of interferon-inducible GTPases to vacuolar pathogens. Thus, GABARAPs are uniquely required for antimicrobial host defense through cytosolic distribution of interferon-inducible GTPases.

Original languageEnglish
Pages (from-to)899-910
Number of pages12
JournalNature Immunology
Volume18
Issue number8
DOIs
Publication statusPublished - 2017 Jul 19
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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