Trafficking-Mediated STING Degradation Requires Sorting to Acidified Endolysosomes and Can Be Targeted to Enhance Anti-tumor Response.

ABSTRACT: STING is an endoplasmic reticulum (ER)-associated transmembrane protein that turns on and quickly turns off downstream signaling as it translocates from the ER to vesicles. How STING signaling is attenuated during trafficking remains poorly understood. Here, we show that trafficking-mediated STING degradation requires ER exit and function of vacuolar ATPase complex. Late-stage STING vesicles are sorted to Rab7-positive endolysosomes for degradation. Based on analysis of existing structures, we also identified the helix amino acid 281 (aa281)-297 as a motif required for trafficking-mediated STING degradation. Immuno-electron microscopy (EM) reveals the size and clustering of STING vesicles and topology of STING on the vesicle. Importantly, blockade of trafficking-mediated STING degradation

SUBMITTER: Gonugunta VK 

PROVIDER: S-EPMC5905341 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature