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Immunology

STING is ESCRTed to degradation by microautophagy

Nature Cell Biology volume 25, pages 379–380 (2023)Cite this article

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Activation of a crucial immune adaptor protein, STING, is tightly regulated by subcellular trafficking, but how it is deactivated remains less well defined. A study now shows that ESCRT-dependent encapsulation of STING-carrying vesicles by lysosomal compartments — through the process of microautophagy — mediates the termination of STING signalling.

Using high-resolution Airyscan confocal microscopy, the authors showed that, after activation, STING could be found inside the lumen of compartments expressing lysosome-associated membrane protein 1 (LAMP1). Next, they used correlative light and electron microscopy (CLEM) to reveal that these compartments use direct encapsulation to engulf STING-bearing vesicles that express markers of recycling endosomes (REs) (suggesting that they originate from REs). Moreover, knockdown of the autophagy protein ATG5 and pharmaceutical inhibition of macroautophagy did not block STING degradation. Together, these data led to the conclusion that degradation of STING occurs through microautophagy and not conventional macroautophagy. Previous studies have suggested that autophagy is central for post-stimulation degradation of STING, and that activated TBK1 protein phosphorylates the autophagy cargo receptor p62 to increase its affinity for ubiquitinated STING6. Earlier studies also showed that STING activates non-canonical autophagy7,8. The new study5 adds important information by explaining the nature of the autophagic process that links STING to lysosomal degradation.

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Fig. 1: Degradation of STING by ESCRT-mediated microautophagy.

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  1. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Sonia Assil & Søren R. Paludan

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  1. Sonia Assil
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  2. Søren R. Paludan
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Correspondence to Søren R. Paludan.

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Assil, S., Paludan, S.R. STING is ESCRTed to degradation by microautophagy. Nat Cell Biol 25, 379–380 (2023). https://doi.org/10.1038/s41556-022-01084-7

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  • DOI: https://doi.org/10.1038/s41556-022-01084-7

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