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Activated STING1 rides the Rafeesome.

Yaping Han1, Jianfei Zheng1, Liang Ge1

  • 1The State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University-Peking University Joint Center for Life Sciences, Tsinghua University, Beijing, China.

Autophagy
|August 6, 2023
PubMed
Summary
This summary is machine-generated.

Secretory autophagy facilitates cargo release without lysosomal degradation. STING1 protein secretion via the rafeesome organelle, involving RAB22A, can promote antitumor immunity.

Keywords:
AutophagosomeERGICRAB22RafeesomeSTINGUnconventional secretion

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Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Non-canonical autophagy utilizes autophagy machinery for non-lysosomal degradation pathways.
  • Secretory autophagy is a non-canonical pathway for cargo secretion.
  • STING1 protein is involved in innate immunity and inflammation.

Purpose of the Study:

  • To investigate the role of secretory autophagy in STING1 protein secretion.
  • To identify the mechanism and organelle involved in STING1 secretion.
  • To explore the immunological consequences of secreted STING1.

Main Methods:

  • Investigated STING1 as a substrate of secretory autophagy.
  • Characterized the rafeesome organelle formation via RAB22A-mediated autophagosomes and early endosomes.
  • Assessed the immunogenicity of extracellular vesicles containing STING1.

Main Results:

  • STING1 is a novel substrate of secretory autophagy.
  • STING1 secretion is mediated by the rafeesome, a RAB22A-dependent organelle.
  • Extracellular vesicles containing STING1 induce antitumor immunity.

Conclusions:

  • Secretory autophagy and the rafeesome pathway are critical for STING1 secretion.
  • RAB22A plays a role in STING1 secretion and potentially in STING1-mediated antitumor immunity.
  • Secreted STING1 in extracellular vesicles can activate antitumor immune responses.