| Autor: |
Segala G; Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland., Bennesch MA; Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland., Ghahhari NM; Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland., Pandey DP; Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland.; Department of Molecular Microbiology, Oslo University Hospital, 0372, Oslo, Norway., Echeverria PC; Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland., Karch F; Département de Génétique et Évolution, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland., Maeda RK; Département de Génétique et Évolution, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland., Picard D; Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211, Genève, Switzerland. didier.picard@unige.ch. |
| Abstrakt: |
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. |
