{"title":"分子伴侣 CCT 的 CCTδ 亚基是 p150Glued 在有丝分裂过程中正确定位到纺锤体两极的必要条件","authors":"Carmen M. Córdoba-Beldad, Julie Grantham","doi":"10.1016/j.ejcb.2024.151430","DOIUrl":null,"url":null,"abstract":"<div><p>Chaperonin Containing Tailless complex polypeptide 1 (CCT) is a molecular chaperone composed of eight distinct subunits that can exist as individual monomers or as components of a double oligomeric ring, which is essential for the folding of actin and tubulin and other substrates. Here we assess the role of CCT subunits in the context of cell cycle progression by individual subunit depletions upon siRNA treatment in mammalian cells. The depletion of individual CCT subunits leads to variation in the distribution of cell cycle phases and changes in mitotic index. Mitotic defects, such as unaligned chromosomes occur when CCTδ is depleted, concurrent with a reduction in spindle pole-localised p150<sup>Glued</sup>, a component of the dynactin complex and a binding partner of monomeric CCTδ. In CCTδ-depleted cells, changes in the elution profile of p150<sup>Glued</sup> are observed consistent with altered conformations and or assembly states with the dynactin complex. Addition of monomeric CCTδ, in the form of GFP-CCTδ, restores correct p150<sup>Glued</sup> localisation to the spindle poles and rescues the mitotic segregation defects that occur when CCTδ is depleted. This study demonstrates a requirement for CCTδ in its monomeric form for correct chromosome segregation via a mechanism that promotes the correct localisation of p150<sup>Glued</sup>, thus revealing further complexities to the interplay between CCT, tubulin folding and microtubule dynamics.</p></div>","PeriodicalId":12010,"journal":{"name":"European journal of cell biology","volume":"103 3","pages":"Article 151430"},"PeriodicalIF":4.3000,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171933524000475/pdfft?md5=b46adc17cb28a7c1e9e5f3c7d7ba6f8f&pid=1-s2.0-S0171933524000475-main.pdf","citationCount":"0","resultStr":"{\"title\":\"The CCTδ subunit of the molecular chaperone CCT is required for correct localisation of p150Glued to spindle poles during mitosis\",\"authors\":\"Carmen M. Córdoba-Beldad, Julie Grantham\",\"doi\":\"10.1016/j.ejcb.2024.151430\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Chaperonin Containing Tailless complex polypeptide 1 (CCT) is a molecular chaperone composed of eight distinct subunits that can exist as individual monomers or as components of a double oligomeric ring, which is essential for the folding of actin and tubulin and other substrates. Here we assess the role of CCT subunits in the context of cell cycle progression by individual subunit depletions upon siRNA treatment in mammalian cells. The depletion of individual CCT subunits leads to variation in the distribution of cell cycle phases and changes in mitotic index. Mitotic defects, such as unaligned chromosomes occur when CCTδ is depleted, concurrent with a reduction in spindle pole-localised p150<sup>Glued</sup>, a component of the dynactin complex and a binding partner of monomeric CCTδ. In CCTδ-depleted cells, changes in the elution profile of p150<sup>Glued</sup> are observed consistent with altered conformations and or assembly states with the dynactin complex. Addition of monomeric CCTδ, in the form of GFP-CCTδ, restores correct p150<sup>Glued</sup> localisation to the spindle poles and rescues the mitotic segregation defects that occur when CCTδ is depleted. This study demonstrates a requirement for CCTδ in its monomeric form for correct chromosome segregation via a mechanism that promotes the correct localisation of p150<sup>Glued</sup>, thus revealing further complexities to the interplay between CCT, tubulin folding and microtubule dynamics.</p></div>\",\"PeriodicalId\":12010,\"journal\":{\"name\":\"European journal of cell biology\",\"volume\":\"103 3\",\"pages\":\"Article 151430\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-06-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0171933524000475/pdfft?md5=b46adc17cb28a7c1e9e5f3c7d7ba6f8f&pid=1-s2.0-S0171933524000475-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European journal of cell biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0171933524000475\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of cell biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0171933524000475","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
The CCTδ subunit of the molecular chaperone CCT is required for correct localisation of p150Glued to spindle poles during mitosis
Chaperonin Containing Tailless complex polypeptide 1 (CCT) is a molecular chaperone composed of eight distinct subunits that can exist as individual monomers or as components of a double oligomeric ring, which is essential for the folding of actin and tubulin and other substrates. Here we assess the role of CCT subunits in the context of cell cycle progression by individual subunit depletions upon siRNA treatment in mammalian cells. The depletion of individual CCT subunits leads to variation in the distribution of cell cycle phases and changes in mitotic index. Mitotic defects, such as unaligned chromosomes occur when CCTδ is depleted, concurrent with a reduction in spindle pole-localised p150Glued, a component of the dynactin complex and a binding partner of monomeric CCTδ. In CCTδ-depleted cells, changes in the elution profile of p150Glued are observed consistent with altered conformations and or assembly states with the dynactin complex. Addition of monomeric CCTδ, in the form of GFP-CCTδ, restores correct p150Glued localisation to the spindle poles and rescues the mitotic segregation defects that occur when CCTδ is depleted. This study demonstrates a requirement for CCTδ in its monomeric form for correct chromosome segregation via a mechanism that promotes the correct localisation of p150Glued, thus revealing further complexities to the interplay between CCT, tubulin folding and microtubule dynamics.
期刊介绍:
The European Journal of Cell Biology, a journal of experimental cell investigation, publishes reviews, original articles and short communications on the structure, function and macromolecular organization of cells and cell components. Contributions focusing on cellular dynamics, motility and differentiation, particularly if related to cellular biochemistry, molecular biology, immunology, neurobiology, and developmental biology are encouraged. Manuscripts describing significant technical advances are also welcome. In addition, papers dealing with biomedical issues of general interest to cell biologists will be published. Contributions addressing cell biological problems in prokaryotes and plants are also welcome.