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Structuring of the yeast endolysosomal pathway by the Rab5 guanine nucleotide exchange factors Muk1 and Vps9

Item Type:Article
Title:Structuring of the yeast endolysosomal pathway by the Rab5 guanine nucleotide exchange factors Muk1 and Vps9
Creators Name:Nesterova, Alexandra, Prosser, Derek C., Welke, Robert-William, Esch, Bianca M., Fröhlich, Florian, Sommer, Thomas, Langemeyer, Lars and Ungermann, Christian
Abstract:The endolysosomal pathway, with its interconnected endosomes and lysosomes, has keyfunctions in cellular nutrient and ion uptake, metabolic adaptation, as well as protein andorganelle turnover via autophagy. Rab5 GTPases are organelle identity markers onendosomes, though it remains unclear why cells have several Rab5 isoforms and guaninenucleotide exchange factors (GEFs) as their activators. Using yeast, we demonstrate thatthe key Rab5 GEFs Vps9 and Muk1 overlap in their Rab5 specificity in vitro but coverdistinct cellular territories in vivo. Vps9 functions between the Golgi and endosomes, whileMuk1 is primarily found in the early endocytic pathway. Using targeting approaches, weshow that Rab5 GEFs can only partially replace each other, demonstrating that each GEF isspecific for its cellular niche. Intriguingly, Muk1 functions in vivo as an oligomer through itsC-terminal domain, which is sufficient to also oligomerize a chimeric Vps9. Overall, our datasuggest the spatial distribution of Rab5 GEFs and their substrate Rab5s fine-tune theendolysosomal system for cellular needs and metabolic cues.
Keywords:Rab5, Vps21, Muk1, Vps9, GEF, Endosome, Lysosome, Vacuole
Source:Molecular Biology of the Cell
ISSN:1059-1524
Publisher:American Society for Cell Biology
Page Range:mbcE25120585
Date:28 January 2026
Official Publication:https://doi.org/10.1091/mbc.e25-12-0585
PubMed:View item in PubMed

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