title: Ypt31/32 GTPases and their novel F-box effector protein Rcy1 regulate protein recycling.
abstract: Ypt/Rab GTPases control various aspects of vesicle formation and targeting via their diverse effectors. We report a new role for these GTPases in protein recycling through a novel effector. The F-box protein Rcy1, which mediates plasma membrane recycling, is identified here as a downstream effector of the Ypt31/32 GTPase pair because it binds active GTP-bound Ypt31/32 and colocalizes with these GTPases on late Golgi and endosomes. Furthermore, Ypt31/32 regulates the polarized localization and half-life of Rcy1. This suggests that Ypt/Rabs can regulate the protein level of their effectors, in addition to the established ways by which they control their effectors. We show that like Rcy1, Ypt31/32 regulate the coupled phosphorylation and recycling of the plasma membrane v-SNARE Snc1. Moreover, Ypt31/32 and Rcy1 regulate the recycling of the furin-homolog Kex2 to the Golgi. Therefore, Ypt31/32 and Rcy1 mediate endosome-to-Golgi transport, because this is the only step shared by Snc1 and Kex2. Finally, we show that Rcy1 physically interacts with Snc1. Based on this result and because F-box proteins serve as adaptors between specific substrates and ubiquitin ligases, we propose that Ypt31/32 GTPases regulate the function of Rcy1 in the phosphorylation and/or ubiquitination of proteins that recycle through the Golgi.
authors.affiliation: Department of Biological Sciences, Laboratory for Molecular Biology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Shu Hui
authors.initials: SH
authors.lastname: Chen
authors.forename: Shan
authors.initials: S
authors.lastname: Chen
authors.forename: Andrei A
authors.initials: AA
authors.lastname: Tokarev
authors.forename: Fengli
authors.initials: F
authors.lastname: Liu
authors.forename: Gregory
authors.initials: G
authors.lastname: Jedd
authors.forename: Nava
authors.initials: N
authors.lastname: Segev
mesh_terms: D015153:Blotting, Western; D011992:Endosomes / Q000378:metabolism; D044783:F-Box Proteins; D005982:Glutathione Transferase / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D043484:Proprotein Convertases / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D050683:R-SNARE Proteins; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D013347:Subcellular Fractions; D013696:Temperature; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000502:physiology*
chemical_list: D044783:F-Box Proteins; D008565:Membrane Proteins; D050683:R-SNARE Proteins; C407703:RCY1 protein, S cerevisiae; C083241:SNC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D033921:Vesicular Transport Proteins; D005982:Glutathione Transferase; D043484:Proprotein Convertases; C058751:KEX2 protein, S cerevisiae; C087905:YPT31 protein, S cerevisiae; C121633:YPT32 protein, S cerevisiae; D020691:rab GTP-Binding Proteins