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Dedicated SNARE s and specialized TRIM cargo receptors mediate secretory autophagy
Author(s) -
Kimura Tomonori,
Jia Jingyue,
Kumar Suresh,
Choi Seong Won,
Gu Yuexi,
Mudd Michal,
Dupont Nicolas,
Jiang Shanya,
Peters Ryan,
Farzam Farzin,
Jain Ashish,
Lidke Keith A,
Adams Christopher M,
Johansen Terje,
Deretic Vojo
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695081
Subject(s) - biology , trim , microbiology and biotechnology , receptor , autophagy , genetics , apoptosis , computer science , operating system
Abstract Autophagy is a process delivering cytoplasmic components to lysosomes for degradation. Autophagy may, however, play a role in unconventional secretion of leaderless cytosolic proteins. How secretory autophagy diverges from degradative autophagy remains unclear. Here we show that in response to lysosomal damage, the prototypical cytosolic secretory autophagy cargo IL ‐1β is recognized by specialized secretory autophagy cargo receptor TRIM 16 and that this receptor interacts with the R‐ SNARE Sec22b to recruit cargo to the LC 3‐ II + sequestration membranes. Cargo secretion is unaffected by downregulation of syntaxin 17, a SNARE promoting autophagosome–lysosome fusion and cargo degradation. Instead, Sec22b in combination with plasma membrane syntaxin 3 and syntaxin 4 as well as SNAP ‐23 and SNAP ‐29 completes cargo secretion. Thus, secretory autophagy utilizes a specialized cytosolic cargo receptor and a dedicated SNARE system. Other unconventionally secreted cargo, such as ferritin, is secreted via the same pathway.