蛋白酶介导的Par2激活在斑马鱼卵激活和卵裂球分裂过程中引发钙波。

IF 7.2 1区 生物学 Q1 Agricultural and Biological Sciences
PLoS Biology Pub Date : 2025-06-17 eCollection Date: 2025-06-01 DOI:10.1371/journal.pbio.3003181
Jiajia Ma, Tom J Carney
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引用次数: 0

摘要

动物发育的成功启动需要在配子原核融合之前立即激活卵子。在所有的分类群中,这都是由钙瞬态波开始的,钙瞬态波穿过卵。在囊胚细胞分裂后期,卵裂沟处也会出现钙波。钙通过肌醇-1,4,5-三磷酸(IP3)受体的激活从内质网释放。在脊椎动物卵子激活过程中,只有一小部分机制被定义为产生IP3,有强有力的证据表明存在其他关键机制。丝氨酸蛋白酶长期以来一直与卵子的激活和受精有关。在这里,我们报道用丝氨酸蛋白酶抑制剂处理斑马鱼卵会导致钙波传播缺陷和卵子激活失败。我们进一步表明,斑马鱼蛋白酶激活受体2a (Par2a)的突变也会导致卵子激活的严重破坏,导致绒毛膜升高和卵浆分离失败。温和的par2a突变进一步发展,但随后表现出异常的卵裂球分裂。我们观察到par2a突变体表现出钙瞬变的幅度和持续时间减少。恢复Ca++或直接注射IP3配体可以恢复丝氨酸蛋白酶抑制剂处理或Par2a突变导致的卵子活化。因此,我们发现丝氨酸蛋白酶活性是斑马鱼卵激活过程中IP3和随后的钙波扩增的关键调节因子,并将其与通过蛋白酶受体Par2a的细胞内钙释放联系起来。这构成了一个新的信号通路,对成功受精至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protease-mediated activation of Par2 elicits calcium waves during zebrafish egg activation and blastomere cleavage.

Successful initiation of animal development requires activation of the egg immediately prior to fusion of gamete pronuclei. In all taxa, this is initiated by waves of calcium transients which transverse across the egg. Calcium waves also occur at cleavage furrows during later blastula cytokinesis. Calcium is released from the endoplasmic reticulum through activation of inositol-1,4,5-trisphosphate (IP3) receptors. Only a subset of the mechanisms employed to generate IP3 during vertebrate egg activation are defined, with strong evidence that other critical mechanisms exist. Serine proteases have been long implicated in egg activation and fertilization. Here, we report that treatment of zebrafish eggs with serine protease inhibitors leads to defective calcium wave propagation and failed egg activation. We further show that mutation of zebrafish Protease-activated receptor 2a (Par2a) also results in severe disruption of egg activation, leading to failed chorion elevation and ooplasmic segregation. Milder par2a mutants progress further, but then show abnormal blastomere cleavage. We observed that par2a mutants show decreased amplitude and duration of calcium transients. Restoring Ca++ or direct injection of IP3 ligand rescues egg activation aborted by either serine protease inhibitor treatment or by mutation of Par2a. We thus show that serine protease activity is a critical regulator of IP3 and subsequent calcium wave amplification during zebrafish egg activation, and link this to intracellular calcium release via the protease receptor, Par2a. This constitutes a novel signaling pathway critical for successful fertilization.

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来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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