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肿瘤抑制因子群岛 E3 连接酶在果蝇睾丸精细胞分化中是必需的。

The tumor suppressor archipelago E3 ligase is required for spermatid differentiation in Drosophila testis.

机构信息

Department of Genetics, University of Szeged, Szeged, Hungary.

Department of Anatomy, Cell and Developmental Biology, Eötvös Lóránd University of Science, Budapest, Hungary.

出版信息

Sci Rep. 2021 Apr 19;11(1):8422. doi: 10.1038/s41598-021-87656-3.

DOI:10.1038/s41598-021-87656-3
PMID:33875704
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8055871/
Abstract

The human orthologue of the tumor suppressor protein FBW7 is encoded by the Drosophila archipelago (ago) gene. Ago is an F-box protein that gives substrate specificity to its SCF ubiquitin ligase complex. It has a central role in multiple biological processes in a tissue-specific manner such as cell proliferation, cellular differentiation, hypoxia-induced gene expression. Here we present a previously unknown tissue-specific role of Ago in spermatid differentiation. We identified a classical mutant of ago which is semi-lethal and male-sterile. During the characterization of ago function in testis, we found that ago plays role in spermatid development, following meiosis. We confirmed spermatogenesis defects by silencing ago by RNAi in testes. The ago mutants show multiple abnormalities in elongating and elongated spermatids, including aberration of the cyst morphology, malformed mitochondrial structures, and individualization defects. Additionally, we determined the subcellular localization of Ago protein with mCherry-Ago transgene in spermatids. Our findings highlight the potential roles of Ago in different cellular processes of spermatogenesis, like spermatid individualization, and regulation of mitochondrial morphology.

摘要

肿瘤抑制蛋白 FBW7 的人类同源物由果蝇 archipelago（ago）基因编码。Ago 是一种 F-box 蛋白，赋予其 SCF 泛素连接酶复合物底物特异性。它以组织特异性的方式在多种生物学过程中发挥核心作用，如细胞增殖、细胞分化、缺氧诱导基因表达。在这里，我们提出了 Ago 在精子细胞分化中一个以前未知的组织特异性作用。我们鉴定了一个经典的 ago 突变体，它是半致死的和雄性不育的。在睾丸中鉴定 ago 功能的过程中，我们发现 ago 在减数分裂后参与精子细胞的发育。我们通过在睾丸中用 RNAi 沉默 ago 来证实精子发生缺陷。ago 突变体在伸长和伸长的精子细胞中显示出多种异常，包括囊泡形态的异常、线粒体结构的畸形和个体化缺陷。此外，我们还通过 mCherry-Ago 转基因在精子细胞中确定了 Ago 蛋白的亚细胞定位。我们的研究结果强调了 Ago 在精子发生的不同细胞过程中的潜在作用，如精子细胞个体化和调节线粒体形态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/a51964a84459/41598_2021_87656_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/3a9588a08690/41598_2021_87656_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/1926492cc08f/41598_2021_87656_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/ead2ae12799b/41598_2021_87656_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/a51964a84459/41598_2021_87656_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/3a9588a08690/41598_2021_87656_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/1926492cc08f/41598_2021_87656_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/ead2ae12799b/41598_2021_87656_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/957f/8055871/a51964a84459/41598_2021_87656_Fig4_HTML.jpg

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