title: Fertilization-induced K63-linked ubiquitylation mediates clearance of maternal membrane proteins.
abstract: In Caenorhabditis elegans, fertilization triggers endocytosis and rapid turnover of maternal surface membrane proteins in lysosomes, although the precise mechanism of this inducible endocytosis is unknown. We found that high levels of K63-linked ubiquitin chains transiently accumulated on endosomes upon fertilization. Endocytosis and the endosomal accumulation of ubiquitin were both regulated downstream of the anaphase-promoting complex, which drives the oocyte's meiotic cell cycle after fertilization. The clearance of maternal membrane proteins and the accumulation of K63-linked ubiquitin on endosomes depended on UBC-13 and UEV-1, which function as an E2 complex that specifically mediates chain elongation of K63-linked polyubiquitin. CAV-1-GFP, an endocytic cargo protein, was modified with K63-linked polyubiquitin in a UBC-13/UEV-1-dependent manner. In ubc-13 or uev-1 mutants, CAV-1-GFP and other membrane proteins were internalized from the plasma membrane normally after fertilization. However, they were not efficiently targeted to the multivesicular body (MVB) pathway but recycled to the cell surface. Our results suggest that UBC-13-dependent K63-linked ubiquitylation is required for proper MVB sorting rather than for internalization. These results also demonstrate a developmentally controlled function of K63-linked ubiquitylation.
authors.affiliation: Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Sato
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Konuma
authors.forename: Katsuya
authors.initials: K
authors.lastname: Sato
authors.forename: Kotone
authors.initials: K
authors.lastname: Tomura
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D022461:Caveolins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D005306:Fertilization; D017238:Genes, Helminth; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D015053:Zygote / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D022461:Caveolins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; C559057:Uev-1 protein, C elegans; D044763:Ubiquitin-Conjugating Enzymes
keywords: Endocytosis; K63-linked ubiquitin chains; Multivesicular body (MVB) pathway; Oocyte-to-zygote transition; Ubc13