Published October 2, 2020 | Version v1
Preprint Open

ER-embedded UBE2J1/RNF26 ubiquitylation complex in spatiotemporal control of the endolysosomal pathway

  • 1. Department of Cell and Chemical Biology, Leiden University Medical Center LUMC, Einthovenweg 20, 2300RC Leiden, NL

Description

The endolysosomal system fulfills a wide variety of cellular functions, many of which are modulated through interactions with other organelles. In particular, the ER exerts spatiotemporal constraints on the organization and motility of endosomes and lysosomes. We have recently described the ER transmembrane E3 ubiquitin ligase RNF26 to control perinuclear positioning and transport dynamics of the endolysosomal vesicular network. We now report that the ubiquitin conjugating enzyme UBE2J1, also anchored in the ER membrane, collaborates with RNF26 in this context, and that the cellular activity of this E2/E3 pair, localized in a perinuclear ER subdomain, is underpinned by transmembrane interactions. Through modification of its substrate SQSTM1/p62, the ER-embedded UBE2J1/RNF26 ubiquitylation complex recruits endosomal adaptors to immobilize their cognate vesicles in the perinuclear region. The resulting spatiotemporal compartmentalization of the endolysosomal system between the perinuclear vesicle cloud and the cell periphery facilitates timely downregulation of endocytosed cargoes, such as EGFR.

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Additional details

Funding

UbiCODE – European Research Training to Decipher The Ub Code : identification of potential biomarkers and drug targets 765445
European Commission