論文 - 詳細
| RRC ID | 55865 |
|---|---|
| 著者 | Chen D, Yang C, Liu S, Hang W, Wang X, Chen J, Shi A. |
| タイトル | SAC-1 ensures epithelial endocytic recycling by restricting ARF-6 activity. |
| ジャーナル | J Cell Biol |
| Abstract |
Arf6/ARF-6 is a crucial regulator of the endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) pool in endocytic recycling. To further characterize ARF-6 regulation, we performed an ARF-6 interactor screen in Caenorhabditis elegans and identified SAC-1, the homologue of the phosphoinositide phosphatase Sac1p in yeast, as a novel ARF-6 partner. In the absence of ARF-6, basolateral endosomes show a loss of SAC-1 staining in epithelial cells. Steady-state cargo distribution assays revealed that loss of SAC-1 specifically affected apical secretory delivery and basolateral recycling. PI(4,5)P2 levels and the endosomal labeling of the ARF-6 effector UNC-16 were significantly elevated in sac-1 mutants, suggesting that SAC-1 functions as a negative regulator of ARF-6. Further analyses revealed an interaction between SAC-1 and the ARF-6-GEF BRIS-1. This interaction outcompeted ARF-6(guanosine diphosphate [GDP]) for binding to BRIS-1 in a concentration-dependent manner. Consequently, loss of SAC-1 promotes the intracellular overlap between ARF-6 and BRIS-1. BRIS-1 knockdown resulted in a significant reduction in PI(4,5)P2 levels in SAC-1-depleted cells. Interestingly, the action of SAC-1 in sequestering BRIS-1 is independent of SAC-1's catalytic activity. Our results suggest that the interaction of SAC-1 with ARF-6 curbs ARF-6 activity by limiting the access of ARF-6(GDP) to its guanine nucleotide exchange factor, BRIS-1. |
| 巻・号 | 217(6) |
| ページ | 2121-2139 |
| 公開日 | 2018-6-4 |
| DOI | 10.1083/jcb.201711065 |
| PII | jcb.201711065 |
| PMID | 29563216 |
| PMC | PMC5987724 |
| MeSH | ADP-Ribosylation Factor 6 ADP-Ribosylation Factors Animals Biocatalysis Caenorhabditis elegans / cytology* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Clathrin / metabolism Endocytosis* Endosomes / metabolism Epithelial Cells / cytology* Epithelial Cells / metabolism* Esterases Green Fluorescent Proteins / metabolism Guanine Nucleotide Exchange Factors / metabolism Guanosine Triphosphate / metabolism HeLa Cells Humans Intestinal Mucosa / metabolism Membrane Proteins Mutant Proteins / metabolism Mutation / genetics Phosphatidylinositol 4,5-Diphosphate / metabolism Protein Binding Protein Domains Protein Transport Secretory Vesicles / metabolism |
| IF | 8.891 |
| 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 | 21 |
| 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 | tm1447 |