title: Dedicated SNAREs and specialized TRIM cargo receptors mediate secretory autophagy.
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 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.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Jingyue
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Seong Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Yuexi
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Mudd
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupont
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Shanya
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Peters
authors.affiliation: Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Farzin
authors.initials: F
authors.lastname: Farzam
authors.affiliation: Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, Tromsø, Norway.
authors.forename: Ashish
authors.identifier: 0000-0001-6549-2788
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Lidke
authors.affiliation: Stanford University Mass Spectrometry, Stanford University, Stanford, CA, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Adams
authors.affiliation: Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, Tromsø, Norway.
authors.forename: Terje
authors.identifier: 0000-0003-1451-9578
authors.initials: T
authors.lastname: Johansen
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA vderetic@salud.unm.edu.
authors.forename: Vojo
authors.initials: V
authors.lastname: Deretic
mesh_terms: D001343:Autophagy; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000378:metabolism; D050766:Qb-SNARE Proteins / Q000378:metabolism; D050767:Qc-SNARE Proteins / Q000378:metabolism; D050683:R-SNARE Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; C100493:SNAP23 protein, human; C432420:SNAP29 protein, human; C572028:Sec22B protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D005293:Ferritins; C117731:TRIM16 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: autophagy; galectins; inflammasome; lysosome; tuberculosis