論文 - 詳細
| RRC ID | 53905 |
|---|---|
| 著者 | Pascual-Ortiz M, Saiardi A, Walla E, Jakopec V, Künzel NA, Span I, Vangala A, Fleig U. |
| タイトル | Asp1 Bifunctional Activity Modulates Spindle Function via Controlling Cellular Inositol Pyrophosphate Levels in Schizosaccharomyces pombe. |
| ジャーナル | Mol Cell Biol |
| Abstract |
The generation of two daughter cells with the same genetic information requires error-free chromosome segregation during mitosis. Chromosome transmission fidelity is dependent on spindle structure/function, which requires Asp1 in the fission yeast Schizosaccharomyces pombe Asp1 belongs to the diphosphoinositol pentakisphosphate kinase (PPIP5K)/Vip1 family which generates high-energy inositol pyrophosphate (IPP) molecules. Here, we show that Asp1 is a bifunctional enzyme in vivo: Asp1 kinase generates specific IPPs which are the substrates of the Asp1 pyrophosphatase. Intracellular levels of these IPPs directly correlate with microtubule stability: pyrophosphatase loss-of-function mutants raised Asp1-made IPP levels 2-fold, thus increasing microtubule stability, while overexpression of the pyrophosphatase decreased microtubule stability. Absence of Asp1-generated IPPs resulted in an aberrant, increased spindle association of the S. pombe kinesin-5 family member Cut7, which led to spindle collapse. Thus, chromosome transmission is controlled via intracellular IPP levels. Intriguingly, identification of the mitochondrion-associated Met10 protein as the first pyrophosphatase inhibitor revealed that IPPs also regulate mitochondrial distribution. |
| 巻・号 | 38(9) |
| 公開日 | 2018-5-1 |
| DOI | 10.1128/MCB.00047-18 |
| PII | MCB.00047-18 |
| PMID | 29440310 |
| PMC | PMC5902593 |
| MeSH | Chromosome Segregation / physiology Cytoskeletal Proteins / metabolism* Cytoskeletal Proteins / physiology* Inositol Inositol Phosphates / metabolism Inositol Phosphates / physiology Kinesins / metabolism Microtubule-Associated Proteins Microtubules Mitosis / physiology Multifunctional Enzymes Phosphotransferases (Phosphate Group Acceptor) / metabolism Pyrophosphatases Schizosaccharomyces Schizosaccharomyces pombe Proteins / metabolism* Schizosaccharomyces pombe Proteins / physiology* Spindle Apparatus / metabolism* Spindle Apparatus / physiology Sulfite Reductase (NADPH) / metabolism |
| IF | 3.611 |
| 引用数 | 5 |
| 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 | 3 |
| 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 | |
| 酵母 | FY8347 FY17673 FY18583 |