論文 - 詳細
| RRC ID | 59388 |
|---|---|
| 著者 | Morris C, Foster OK, Handa S, Peloza K, Voss L, Somhegyi H, Jian Y, Vo MV, Harp M, Rambo FM, Yang C, Hermann GJ. |
| タイトル | Function and regulation of the Caenorhabditis elegans Rab32 family member GLO-1 in lysosome-related organelle biogenesis. |
| ジャーナル | PLoS Genet |
| Abstract |
Cell type-specific modifications of conventional endosomal trafficking pathways lead to the formation of lysosome-related organelles (LROs). C. elegans gut granules are intestinally restricted LROs that coexist with conventional degradative lysosomes. The formation of gut granules requires the Rab32 family member GLO-1. We show that the loss of glo-1 leads to the mistrafficking of gut granule proteins but does not significantly alter conventional endolysosome biogenesis. GLO-3 directly binds to CCZ-1 and they both function to promote the gut granule association of GLO-1, strongly suggesting that together, GLO-3 and CCZ-1 activate GLO-1. We found that a point mutation in GLO-1 predicted to spontaneously activate, and function independently of it guanine nucleotide exchange factor (GEF), localizes to gut granules and partially restores gut granule protein localization in ccz-1(-) and glo-3(-) mutants. CCZ-1 forms a heterodimeric complex with SAND-1(MON1), which does not function in gut granule formation, to activate RAB-7 in trafficking pathways to conventional lysosomes. Therefore, our data suggest a model whereby the function of a Rab GEF can be altered by subunit exchange. glo-3(-) mutants, which retain low levels of GLO-3 activity, generate gut granules that lack GLO-1 and improperly accumulate RAB-7 in a SAND-1 dependent process. We show that GLO-1 and GLO-3 restrict the distribution of RAB-7 to conventional endolysosomes, providing insights into the segregation of pathways leading to conventional lysosomes and LROs. |
| 巻・号 | 14(11) |
| ページ | e1007772 |
| 公開日 | 2018-11-1 |
| DOI | 10.1371/journal.pgen.1007772 |
| PII | PGENETICS-D-18-00362 |
| PMID | 30419011 |
| PMC | PMC6268011 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cytoplasmic Granules / metabolism Digestive System / embryology Digestive System / metabolism Genes, Helminth Lysosomes / metabolism Mutation Organelle Biogenesis Protein Interaction Domains and Motifs Vesicular Transport Proteins / chemistry Vesicular Transport Proteins / genetics Vesicular Transport Proteins / metabolism rab GTP-Binding Proteins / chemistry rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism* |
| IF | 5.224 |
| 引用数 | 4 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm920 tm1892 tm1125 tm592 tm2241 |