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Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9

Vps9 and Muk1 are guanine nucleotide exchange factors (GEFs) in Saccharomyces cerevisiae that regulate membrane trafficking in the endolysosomal pathway by activating Rab5 GTPases. We show that Vps9 is the primary Rab5 GEF required for biogenesis of late endosomal multivesicular bodies (MVBs). Howev...

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Detalles Bibliográficos
Autores principales: Shideler, Tess, Nickerson, Daniel P., Merz, Alexey J., Odorizzi, Greg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454180/
https://www.ncbi.nlm.nih.gov/pubmed/25673804
http://dx.doi.org/10.1091/mbc.E14-06-1156
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author Shideler, Tess
Nickerson, Daniel P.
Merz, Alexey J.
Odorizzi, Greg
author_facet Shideler, Tess
Nickerson, Daniel P.
Merz, Alexey J.
Odorizzi, Greg
author_sort Shideler, Tess
collection PubMed
description Vps9 and Muk1 are guanine nucleotide exchange factors (GEFs) in Saccharomyces cerevisiae that regulate membrane trafficking in the endolysosomal pathway by activating Rab5 GTPases. We show that Vps9 is the primary Rab5 GEF required for biogenesis of late endosomal multivesicular bodies (MVBs). However, only Vps9 (but not Muk1) is required for the formation of aberrant class E compartments that arise upon dysfunction of endosomal sorting complexes required for transport (ESCRTs). ESCRT dysfunction causes ubiquitinated transmembrane proteins to accumulate at endosomes, and we demonstrate that endosomal recruitment of Vps9 is promoted by its ubiquitin-binding CUE domain. Muk1 lacks ubiquitin-binding motifs, but its fusion to the Vps9 CUE domain allows Muk1 to rescue endosome morphology, cargo trafficking, and cellular stress-tolerance phenotypes that result from loss of Vps9 function. These results indicate that ubiquitin binding by the CUE domain promotes Vps9 function in endolysosomal membrane trafficking via promotion of localization.
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spelling pubmed-44541802015-06-16 Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9 Shideler, Tess Nickerson, Daniel P. Merz, Alexey J. Odorizzi, Greg Mol Biol Cell Articles Vps9 and Muk1 are guanine nucleotide exchange factors (GEFs) in Saccharomyces cerevisiae that regulate membrane trafficking in the endolysosomal pathway by activating Rab5 GTPases. We show that Vps9 is the primary Rab5 GEF required for biogenesis of late endosomal multivesicular bodies (MVBs). However, only Vps9 (but not Muk1) is required for the formation of aberrant class E compartments that arise upon dysfunction of endosomal sorting complexes required for transport (ESCRTs). ESCRT dysfunction causes ubiquitinated transmembrane proteins to accumulate at endosomes, and we demonstrate that endosomal recruitment of Vps9 is promoted by its ubiquitin-binding CUE domain. Muk1 lacks ubiquitin-binding motifs, but its fusion to the Vps9 CUE domain allows Muk1 to rescue endosome morphology, cargo trafficking, and cellular stress-tolerance phenotypes that result from loss of Vps9 function. These results indicate that ubiquitin binding by the CUE domain promotes Vps9 function in endolysosomal membrane trafficking via promotion of localization. The American Society for Cell Biology 2015-04-01 /pmc/articles/PMC4454180/ /pubmed/25673804 http://dx.doi.org/10.1091/mbc.E14-06-1156 Text en © 2015 Shideler et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Shideler, Tess
Nickerson, Daniel P.
Merz, Alexey J.
Odorizzi, Greg
Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9
title Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9
title_full Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9
title_fullStr Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9
title_full_unstemmed Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9
title_short Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9
title_sort ubiquitin binding by the cue domain promotes endosomal localization of the rab5 gef vps9
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454180/
https://www.ncbi.nlm.nih.gov/pubmed/25673804
http://dx.doi.org/10.1091/mbc.E14-06-1156
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