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Nat Commun. 2019 Apr 23;10(1):1833. doi: 10.1038/s41467-019-09800-y.

Vps11 and Vps18 of Vps-C membrane traffic complexes are E3 ubiquitin ligases and fine-tune signalling.

Author information

1
Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland.
2
Department of Molecular Microbiology, Oslo University Hospital, 0372, Oslo, Norway.
3
Département de Génétique et Évolution, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland.
4
Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland. didier.picard@unige.ch.

Abstract

In response to extracellular signals, many signalling proteins associated with the plasma membrane are sorted into endosomes. This involves endosomal fusion, which depends on the complexes HOPS and CORVET. Whether and how their subunits themselves modulate signal transduction is unknown. We show that Vps11 and Vps18 (Vps11/18), two common subunits of the HOPS/CORVET complexes, are E3 ubiquitin ligases. Upon overexpression of Vps11/Vps18, we find perturbations of ubiquitination in signal transduction pathways. We specifically demonstrate that Vps11/18 regulate several signalling factors and pathways, including Wnt, estrogen receptor α (ERα), and NFκB. For ERα, we demonstrate that the Vps11/18-mediated ubiquitination of the scaffold protein PELP1 impairs the activation of ERα by c-Src. Thus, proteins involved in membrane traffic, in addition to performing their well-described role in endosomal fusion, fine-tune signalling in several different ways, including through ubiquitination.

PMID:
31015428
PMCID:
PMC6478910
DOI:
10.1038/s41467-019-09800-y
[Indexed for MEDLINE]
Free PMC Article

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