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. 2021 Jan 19;34(3):108659.
doi: 10.1016/j.celrep.2020.108659.

The ER-embedded UBE2J1/RNF26 ubiquitylation complex exerts spatiotemporal control over the endolysosomal pathway

Tom Cremer  1 , Marlieke L M Jongsma  1 , Fredrik Trulsson  1 , Alfred C O Vertegaal  1 , Jacques Neefjes  2 , Ilana Berlin  3
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Free article

The ER-embedded UBE2J1/RNF26 ubiquitylation complex exerts spatiotemporal control over the endolysosomal pathway

Tom Cremer et al. Cell Rep. .
Free article

Abstract

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 as a regulator of endolysosomal perinuclear positioning and transport dynamics. Here, we report that the ubiquitin conjugating enzyme UBE2J1, also anchored in the ER membrane, partners with RNF26 in this context, and that the cellular activity of the resulting E2/E3 pair is localized in a perinuclear ER subdomain and supported by transmembrane interactions. Through modification of SQSTM1/p62 on lysine 435, the ER-embedded UBE2J1/RNF26 ubiquitylation complex recruits endosomal adaptors to immobilize their cognate vesicles in the perinuclear region of the cell. The resulting spatiotemporal compartmentalization promotes the trafficking of activated EGFR to lysosomes and facilitates the termination of EGF-induced AKT signaling.

Keywords: Akt; EGFR; RNF26; UBE2J1; endoplasmic reticulum; endosomes; p62; ubiquitin.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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