Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy.
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 TRIM16 and that this receptor interacts with the R-SNARE Sec22b to recruit cargo to the LC3-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.
['Kimura|Tomonori|T|', 'Jia|Jingyue|J|', 'Kumar|Suresh|S|', 'Choi|Seong Won|SW|', 'Gu|Yuexi|Y|', 'Mudd|Michal|M|', 'Dupont|Nicolas|N|', 'Jiang|Shanya|S|', 'Peters|Ryan|R|', 'Farzam|Farzin|F|', 'Jain|Ashish|A|0000-0001-6549-2788', 'Lidke|Keith A|KA|', 'Adams|Christopher M|CM|', 'Johansen|Terje|T|0000-0003-1451-9578', 'Deretic|Vojo|V|']
D001343:Autophagy D002460:Cell Line D004268:DNA-Binding Proteins D005293:Ferritins D006801:Humans D053583:Interleukin-1beta D008869:Microtubule-Associated Proteins D009000:Monocytes D050765:Qa-SNARE Proteins D050766:Qb-SNARE Proteins D050767:Qc-SNARE Proteins D050683:R-SNARE Proteins D014157:Transcription Factors D000070584:Tripartite Motif Proteins D044767:Ubiquitin-Protein Ligases
autophagy lysosome galectins inflammasome tuberculosis