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驱动蛋白-7 中心体蛋白-E 调控顶体的形成和结构维持。

Kinesin-7 CENP-E regulates the formation and structural maintenance of the acrosome.

机构信息

Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350122, Fujian, China.

Key Laboratory of Stem Cell Engineering and Regenerative Medicine, Fujian Province University, Fuzhou, 350122, Fujian, China.

出版信息

Cell Tissue Res. 2021 Mar;383(3):1167-1182. doi: 10.1007/s00441-020-03341-3. Epub 2020 Nov 25.

DOI:10.1007/s00441-020-03341-3
PMID:33237480
Abstract

The acrosome is a special organelle that develops from the Golgi apparatus and the endolysosomal compartment in the spermatids. Centromere protein E (CENP-E) is an essential kinesin motor in chromosome congression and alignment. This study is aimed at investigating the roles and mechanisms of kinesin-7 CENP-E in the formation of the acrosome during spermatogenesis. Male ICR mice are injected with GSK923295 for long-term inhibition of CENP-E. Chemical inhibition and siRNA-mediated knockdown of CENP-E are carried out in the GC-2 spd cells. The morphology of the acrosomes is determined by the HE staining, immunofluorescence, and transmission electron microscopy. We have identified CENP-E is a key factor in the formation and structural maintenance of the acrosome during acrosome biogenesis. Long-term inhibition of CENP-E by GSK923295 results in the asymmetric acrosome and the dispersed acrosome. CENP-E depletion leads to the malformation of the Golgi complex and abnormal targeting of the PICK1- and PIST-positive Golgi-associated vesicles. Our findings uncover an essential role of CENP-E in membrane trafficking and structural organization of the acrosome in the spermatids during spermatogenesis. Our results shed light on the molecular mechanisms involved in vesicle trafficking and architecture maintenance of the acrosome.

摘要

顶体是一个特殊的细胞器,它由精子细胞中的高尔基体和内溶酶体区室发育而来。着丝粒蛋白 E (CENP-E) 是染色体聚合并对齐所必需的驱动蛋白。本研究旨在研究在精子发生过程中顶体形成过程中驱动蛋白-7 CENP-E 的作用和机制。雄性 ICR 小鼠注射 GSK923295 以长期抑制 CENP-E。在 GC-2 spd 细胞中进行 CENP-E 的化学抑制和 siRNA 介导的敲低。通过 HE 染色、免疫荧光和透射电子显微镜确定顶体的形态。我们已经确定 CENP-E 是顶体发生过程中顶体形成和结构维持的关键因素。GSK923295 对 CENP-E 的长期抑制导致顶体不对称和顶体分散。CENP-E 耗竭导致高尔基体复合体的畸形和 PICK1 和 PIST 阳性的高尔基相关囊泡的异常靶向。我们的发现揭示了 CENP-E 在精子发生过程中顶体的膜运输和结构组织中的重要作用。我们的结果阐明了与顶体囊泡运输和结构维持相关的分子机制。

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Cell Tissue Res. 2021 Mar;383(3):1167-1182. doi: 10.1007/s00441-020-03341-3. Epub 2020 Nov 25.
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本文引用的文献

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Kinesin-7 CENP-E regulates chromosome alignment and genome stability of spermatogenic cells.驱动蛋白7 CENP-E调节生精细胞的染色体排列和基因组稳定性。
Cell Death Discov. 2020 Apr 20;6:25. doi: 10.1038/s41420-020-0261-8. eCollection 2020.
2
Mechanism of Acrosome Biogenesis in Mammals.哺乳动物顶体生物发生的机制。
Front Cell Dev Biol. 2019 Sep 18;7:195. doi: 10.3389/fcell.2019.00195. eCollection 2019.
3
Vps13b is required for acrosome biogenesis through functions in Golgi dynamic and membrane trafficking.Vps13b 通过参与高尔基体动态和膜运输过程对顶体发生起作用。
Cell Mol Life Sci. 2020 Feb;77(3):511-529. doi: 10.1007/s00018-019-03192-4. Epub 2019 Jun 19.
4
A tension-independent mechanism reduces Aurora B-mediated phosphorylation upon microtubule capture by CENP-E at the kinetochore.一个张力非依赖的机制降低了着丝粒上 Aurora B 介导的磷酸化作用,该机制是由 CENP-E 在微管捕获时产生的。
Cell Cycle. 2019 Jun;18(12):1349-1363. doi: 10.1080/15384101.2019.1617615. Epub 2019 May 23.
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Microtubule end conversion mediated by motors and diffusing proteins with no intrinsic microtubule end-binding activity.由没有内在微管末端结合活性的马达和扩散蛋白介导的微管末端转换。
Nat Commun. 2019 Apr 11;10(1):1673. doi: 10.1038/s41467-019-09411-7.
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AU040320 deficiency leads to disruption of acrosome biogenesis and infertility in homozygous mutant mice.AU040320 缺乏导致同源突变小鼠顶体生物发生中断和不育。
Sci Rep. 2018 Jul 10;8(1):10379. doi: 10.1038/s41598-018-28666-6.
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Lateral attachment of kinetochores to microtubules is enriched in prometaphase rosette and facilitates chromosome alignment and bi-orientation establishment.动粒的横向附着到微管上在前期花环状结构中富集,并促进染色体的排列和双定向建立。
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