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WHAMM 对于成熟的小鼠卵母细胞纺锤体的形成和纺锤体肌动蛋白聚合是必需的。

WHAMM is essential for spindle formation and spindle actin polymerization in maturing mouse oocytes.

机构信息

Primate Resources Center (PRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Jeongeup-si, Jeollabuk-do, Republic of Korea.

Department of Animal Sciences, Chungbuk National University , Cheong-Ju, Chungcheongbuk-Do, Republic of Korea.

出版信息

Cell Cycle. 2021 Jan;20(2):225-235. doi: 10.1080/15384101.2020.1867791. Epub 2021 Jan 5.

Abstract

WHAMM (WAS Protein Homolog Associated with Actin, Golgi Membranes, and Microtubules) is involved in Golgi membrane association, microtubule binding, and actin nucleation as a nucleation-promoting factor, which activates the actin-related protein 2/3 complex (the Arp2/3 complex). However, the role of WHAMM in mammalian oocyte maturation is poorly understood. The presence of WHAMM mRNA and protein during all stages of mouse oocyte maturation has been verified. It is mainly co-localized with the actin cage permeating the spindle during mouse oocyte maturation. Through the knockdown of WHAMM, we confirmed that it regulates spindle formation and affects the localization of the microtubule-organizing center (MTOC) during the early stages of spindle formation. Moreover, depletion of WHAMM impaired the formation of the spindle actin and chromosome alignment, which might be the cause of chromosomal aneuploidy and abnormal, asymmetric division. Treatment with brefeldin A (BFA), an inhibitor of vesicle transport from the endoplasmic reticulum (ER) to the Golgi apparatus, induced abnormal and dispersed localization of WHAMM. Taken together, these findings show that WHAMM is an essential component of the actin cytoskeleton machinery and plays a crucial role in oocyte maturation, presumably by controlling the formation of spindles with normal length by activating the formation of the spindle actin via the Arp2/3 complex.

摘要

WHAMM(WAS 蛋白同源物与肌动蛋白、高尔基体膜和微管相关)参与高尔基体膜的结合、微管的结合和肌动蛋白的成核作为成核促进因子,从而激活肌动蛋白相关蛋白 2/3 复合物(Arp2/3 复合物)。然而,WHAMM 在哺乳动物卵母细胞成熟中的作用知之甚少。已经验证了 WHAMM mRNA 和蛋白质在小鼠卵母细胞成熟的所有阶段的存在。它主要与贯穿纺锤体的肌动蛋白笼共定位,在小鼠卵母细胞成熟过程中。通过 WHAMM 的敲低,我们证实它调节纺锤体的形成,并在纺锤体形成的早期影响微管组织中心(MTOC)的定位。此外,WHAMM 的耗竭破坏了纺锤体肌动蛋白的形成和染色体的排列,这可能是染色体非整倍体和异常、不对称分裂的原因。用布雷菲德菌素 A(BFA)处理,一种从内质网(ER)到高尔基体的囊泡运输抑制剂,诱导 WHAMM 异常和分散定位。总之,这些发现表明 WHAMM 是肌动蛋白细胞骨架机制的重要组成部分,在卵母细胞成熟中起着关键作用,可能通过激活 Arp2/3 复合物形成正常长度的纺锤体来控制纺锤体的形成。

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