title: Ubiquitin binding by the CUE domain promotes endosomal localization of the Rab5 GEF Vps9.
abstract: 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.
authors: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347.
authors: Tess
authors: T
authors: Shideler
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195-3750 odorizzi@colorado.edu dpn2@u.washington.edu.
authors: Daniel P
authors: DP
authors: Nickerson
authors: Department of Biochemistry, University of Washington, Seattle, WA 98195-3750.
authors: Alexey J
authors: AJ
authors: Merz
authors: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309-0347 odorizzi@colorado.edu dpn2@u.washington.edu.
authors: Greg
authors: G
authors: Odorizzi
mesh_terms: D020816:Amino Acid Motifs; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D057146:Multivesicular Bodies / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D020662:Guanine Nucleotide Exchange Factors; C583270:Muk1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; C099285:VPS9 protein, S cerevisiae; D033921:Vesicular Transport Proteins