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A SPOPL/Cullin-3 ubiquitin ligase complex regulates endocytic trafficking by targeting EPS15 at endosomes.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Gschweitl Michaela, Ulbricht Anna, Barnes Christopher A, Enchev Radoslav I, Stoffel-Studer Ingrid, Meyer-Schaller Nathalie, Huotari Jatta, Yamauchi Yohei, Greber Urs F, Helenius Ari, Peter Matthias,
Project ER-phagy mechanisms to maintain and restore endoplasmic reticulum homeostasis
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Original article (peer-reviewed)

Journal eLife
Volume (Issue) 5
Page(s) 13841 - 13841
Title of proceedings eLife
DOI 10.7554/elife.13841

Open Access

Abstract

Cullin-3 (CUL3)-based ubiquitin ligases regulate endosome maturation and trafficking of endocytic cargo to lysosomes in mammalian cells. Here, we report that these functions depend on SPOPL, a substrate-specific CUL3 adaptor. We find that SPOPL associates with endosomes and is required for both the formation of multivesicular bodies (MVBs) and the endocytic host cell entry of influenza A virus. In SPOPL-depleted cells, endosomes are enlarged and fail to acquire intraluminal vesicles (ILVs). We identify a critical substrate ubiquitinated by CUL3-SPOPL as EPS15, an endocytic adaptor that also associates with the ESCRT-0 complex members HRS and STAM on endosomes. Indeed, EPS15 is ubiquitinated in a SPOPL-dependent manner, and accumulates with HRS in cells lacking SPOPL. Together, our data indicates that a CUL3-SPOPL E3 ubiquitin ligase complex regulates endocytic trafficking and MVB formation by ubiquitinating and degrading EPS15 at endosomes, thereby influencing influenza A virus infection as well as degradation of EGFR and other EPS15 targets.
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