Laura Marín, Jorge Castro-Sangrador, Marta Hoya, Shara Tello, Pedro M Coll, Javier Encinar Del Dedo, Alfonso Fernández-Álvarez, Juan C Ribas, Phong T Tran, Sergio A Rincon
{"title":"PP6磷酸酶和伸长子通过控制微管调节因子的水平来促进激酶5依赖性纺锤体组装。","authors":"Laura Marín, Jorge Castro-Sangrador, Marta Hoya, Shara Tello, Pedro M Coll, Javier Encinar Del Dedo, Alfonso Fernández-Álvarez, Juan C Ribas, Phong T Tran, Sergio A Rincon","doi":"10.1371/journal.pgen.1011596","DOIUrl":null,"url":null,"abstract":"<p><p>Eukaryotic chromosome segregation relies on the assembly of a bipolar machinery based on microtubules (MTs), named the mitotic spindle. Formation of the mitotic spindle follows a force balance mechanism that ensures the proper capture and separation of sister chromatids. Many proteins have been involved in the establishment of this force balance, although kinesin 5 is well recognized as the major outward pushing force generator, since its inactivation results in monopolar, non-functional spindles. In order to find additional players in the force balance mechanism, we have performed a suppressor screen using a conditional allele of the fission yeast kinesin 5 ortholog Cut7. This screen identified that the lack of the PP6 phosphatase partially suppresses cut7 phenotypes, at least by defective translation of MT regulators, such as the minus end-directed kinesin Klp2, the MT stabilizer Alp7 and the MT bundler Ase1, impacting on the force balance mechanism. Additionally, our data show that the Elongator complex, a target activated by PP6 for efficient tRNA modification, also contributes to the force balance, albeit to a lesser extent. Importantly, this complex has recently been implicated in direct MT polymerization in metazoans, a role not shared by its fission yeast counterpart.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 10","pages":"e1011596"},"PeriodicalIF":3.7000,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PP6 phosphatase and Elongator contribute to kinesin 5-dependent spindle assembly by controlling microtubule regulators levels.\",\"authors\":\"Laura Marín, Jorge Castro-Sangrador, Marta Hoya, Shara Tello, Pedro M Coll, Javier Encinar Del Dedo, Alfonso Fernández-Álvarez, Juan C Ribas, Phong T Tran, Sergio A Rincon\",\"doi\":\"10.1371/journal.pgen.1011596\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Eukaryotic chromosome segregation relies on the assembly of a bipolar machinery based on microtubules (MTs), named the mitotic spindle. Formation of the mitotic spindle follows a force balance mechanism that ensures the proper capture and separation of sister chromatids. Many proteins have been involved in the establishment of this force balance, although kinesin 5 is well recognized as the major outward pushing force generator, since its inactivation results in monopolar, non-functional spindles. In order to find additional players in the force balance mechanism, we have performed a suppressor screen using a conditional allele of the fission yeast kinesin 5 ortholog Cut7. This screen identified that the lack of the PP6 phosphatase partially suppresses cut7 phenotypes, at least by defective translation of MT regulators, such as the minus end-directed kinesin Klp2, the MT stabilizer Alp7 and the MT bundler Ase1, impacting on the force balance mechanism. Additionally, our data show that the Elongator complex, a target activated by PP6 for efficient tRNA modification, also contributes to the force balance, albeit to a lesser extent. Importantly, this complex has recently been implicated in direct MT polymerization in metazoans, a role not shared by its fission yeast counterpart.</p>\",\"PeriodicalId\":49007,\"journal\":{\"name\":\"PLoS Genetics\",\"volume\":\"21 10\",\"pages\":\"e1011596\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PLoS Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1371/journal.pgen.1011596\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PLoS Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1371/journal.pgen.1011596","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
PP6 phosphatase and Elongator contribute to kinesin 5-dependent spindle assembly by controlling microtubule regulators levels.
Eukaryotic chromosome segregation relies on the assembly of a bipolar machinery based on microtubules (MTs), named the mitotic spindle. Formation of the mitotic spindle follows a force balance mechanism that ensures the proper capture and separation of sister chromatids. Many proteins have been involved in the establishment of this force balance, although kinesin 5 is well recognized as the major outward pushing force generator, since its inactivation results in monopolar, non-functional spindles. In order to find additional players in the force balance mechanism, we have performed a suppressor screen using a conditional allele of the fission yeast kinesin 5 ortholog Cut7. This screen identified that the lack of the PP6 phosphatase partially suppresses cut7 phenotypes, at least by defective translation of MT regulators, such as the minus end-directed kinesin Klp2, the MT stabilizer Alp7 and the MT bundler Ase1, impacting on the force balance mechanism. Additionally, our data show that the Elongator complex, a target activated by PP6 for efficient tRNA modification, also contributes to the force balance, albeit to a lesser extent. Importantly, this complex has recently been implicated in direct MT polymerization in metazoans, a role not shared by its fission yeast counterpart.
期刊介绍:
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