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化学诱导临近揭示了卵母细胞核膜上依赖 Piezo 的减数分裂检查点。

Chemically induced proximity reveals a Piezo-dependent meiotic checkpoint at the oocyte nuclear envelope.

机构信息

California Institute for Quantitative Biosciences (QB3) and Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA.

Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.

出版信息

Science. 2024 Nov 22;386(6724):eadm7969. doi: 10.1126/science.adm7969.

Abstract

Sexual reproduction relies on robust quality control during meiosis. Assembly of the synaptonemal complex between homologous chromosomes (synapsis) regulates meiotic recombination and is crucial for accurate chromosome segregation in most eukaryotes. Synapsis defects can trigger cell cycle delays and, in some cases, apoptosis. We developed and deployed a chemically induced proximity system to identify key elements of this quality control pathway in . Persistence of the polo-like kinase PLK-2 at pairing centers-specialized chromosome regions that interact with the nuclear envelope-induced apoptosis of oocytes in response to phosphorylation and destabilization of the nuclear lamina. Unexpectedly, the Piezo1/PEZO-1 channel localized to the nuclear envelope and was required to transduce this signal to promote apoptosis in maturing oocytes.

摘要

有性生殖依赖于减数分裂过程中的强大质量控制。同源染色体之间联会复合体(synapsis)的组装调节着减数分裂重组,对于大多数真核生物中染色体的正确分离至关重要。联会缺陷会引发细胞周期延迟,在某些情况下会引发细胞凋亡。我们开发并部署了一种化学诱导的临近系统,以鉴定该质量控制途径在. 中的关键元件。对配对中心(与核膜相互作用的特化染色体区域)的中心体蛋白激酶 PLK-2 的持续存在,引发了卵母细胞的凋亡反应,这种反应是由于核纤层的磷酸化和不稳定导致的。出乎意料的是,Piezo1/PEZO-1 通道定位于核膜,并需要传递此信号以促进成熟卵母细胞的凋亡。

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