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Multiple pools of Protein Phosphatase 2A-B56 function to antagonize spindle assembly, promote kinetochore attachments and maintain cohesion in Drosophila Oocytes
bioRxiv - Genetics Pub Date : 2020-09-06 , DOI: 10.1101/2020.08.01.232512
Janet K. Jang , Amy C. Gladstein , Arunika Das , Zachary L. Sisco , Kim S. McKim

Meiosis in female oocytes lack centrosomes, the major microtubule-organizing center, which makes them especially vulnerable to aneuploidy. In the acentrosomal oocytes of Drosophila, meiotic spindle assembly depends on the chromosomal passenger complex (CPC). Aurora B is the catalytic component of the CPC while the remaining subunits regulate its localization. Using an inhibitor of Aurora B activity, Binucleine 2, we found that continuous Aurora B activity is required to maintain the oocyte spindle during meiosis I, and this activity is antagonized by phosphatases acting on spindle associated proteins such as kinesins. Protein Phosphatase 2A (PP2A) exists in two varieties, B55 and B56. While both antagonize Aurora B, B55 has only minor roles in meiosis I spindle function. The B56 subunit is encoded by two partially redundant paralogs in the Drosophila genome, wdb and wrd. Knocking down both paralogs showed that the B56 subunit is critical for maintaining sister chromatid cohesion, establishing end-on microtubule attachments, and the metaphase I arrest in oocytes. We found that WDB recruitment to the centromeres depends on BUBR1, MEI-S332, and kinetochore protein SPC105R. While BUBR1 has been shown previously to stabilize microtubule attachments in Drosophila oocytes, only SPC105R is required for cohesion maintenance during meiosis I. We propose that SPC105R promotes cohesion maintenance by recruiting two proteins that recruit PP2A, MEI-S332, and the Soronin homolog Dalmatian.

中文翻译:

蛋白磷酸酶2A-B56的多个库可拮抗纺锤体装配,促进线粒体附着并维持果蝇卵母细胞的凝聚力

女性卵母细胞的减数分裂缺乏中心体,中心体是主要的微管组织中心,这使它们特别容易受到非整倍性的影响。在果蝇的中心体卵母细胞中,减数分裂纺锤体组装取决于染色体乘客复合体(CPC)。极光B是CPC的催化成分,而其余的亚基则调节其定位。使用Aurora B活性抑制剂Binucleine 2,我们发现连续的Aurora B活性是减数分裂I期间维持卵母细胞纺锤体所必需的,而这种活性被作用于纺锤体相关蛋白(例如驱动蛋白)的磷酸酶所拮抗。蛋白磷酸酶2A(PP2A)存在两个变体B55和B56。虽然两者都拮抗Aurora B,但B55在减数分裂I纺锤体功能中仅发挥较小作用。B56亚基由果蝇基因组中的两个部分冗余旁系同源物wdb和wrd编码。敲除这两个旁系同源物表明,B56亚基对于维持姐妹染色单体凝聚力,建立末端微管附着以及在卵母细胞中阻滞中期至关重要。我们发现WDB向着丝粒的募集取决于BUBR1,MEI-S332和动粒蛋白SPC105R。虽然以前已经证明BUBR1可以稳定果蝇卵母细胞中的微管附着,但在减数分裂I期间仅需要SPC105R来保持内聚力。我们建议SPC105R通过募集募集PP2A,MEI-S332和Soronin同源达尔马提亚犬的两种蛋白质来促进内聚力的维持。建立末端微管附件,并将中期I停在卵母细胞中。我们发现WDB向着丝粒的募集取决于BUBR1,MEI-S332和动粒蛋白SPC105R。虽然以前已经证明BUBR1可以稳定果蝇卵母细胞中的微管附着,但在减数分裂I期间仅需要SPC105R来保持内聚力。我们建议SPC105R通过募集募集PP2A,MEI-S332和Soronin同源达尔马提亚犬的两种蛋白质来促进内聚力的维持。建立末端微管附件,并将中期I停在卵母细胞中。我们发现WDB向着丝粒的募集取决于BUBR1,MEI-S332和动粒蛋白SPC105R。虽然以前已经证明BUBR1可以稳定果蝇卵母细胞中的微管附着,但在减数分裂I期间仅需要SPC105R来保持内聚力。我们建议SPC105R通过募集募集PP2A,MEI-S332和Soronin同源达尔马提亚犬的两种蛋白质来促进内聚力的维持。
更新日期:2020-09-08
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