The male germline-specific protein MAPS is indispensable for pachynema progression and fertility.
The male germline-specific protein MAPS is indispensable for pachynema progression and fertility.
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DOI：
10.1073/pnas.2025421118
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发表时间：
2021-02-23
影响因子：
11.1
通讯作者：
Liu K
中科院分区：
文献类型：
--
作者：
Li M;Zheng J;Li G;Lin Z;Li D;Liu D;Feng H;Cao D;Ng EHY;Li RHW;Han C;Yeung WSB;Chow LT;Wang H;Liu K
在哺乳动物减数分裂前期，发生了一系列事件，如同源重组、DSB修复、交叉形成、XY小体形成和减数分裂性染色体失活(MSCI)。我们在这里报道了一种雄性厚线虫特异性(MAPS)蛋白在小鼠精母细胞的I期前期进展中是必不可少的。MAPs基因敲除会导致粗线期精母细胞在早、中、晚期死亡，导致男性不育，而不是女性不育。此外，在MAPS−/−粗线期精母细胞中，蛋白质泛素化显著增加，这可能是包括失败的MSCI在内的全球基因表达失调的原因之一。总而言之，MAP是男性生育不可或缺的蛋白质。减数分裂是一种特殊的细胞分裂，从二倍体祖细胞产生单倍体生殖细胞。通过差异RNA表达分析，我们以前发现了一些小鼠基因在精母细胞中显著升高，而在精原细胞和体细胞器官中表达很低。在这里，我们详细研究了这些基因之一的1700102P08Rik，并独立得出结论，它编码一种男性生殖系特有的蛋白，这与最近的一份报告一致。我们证明了它在精母细胞中对厚线虫的发展是必不可少的，并将其命名为男性厚线虫特异性蛋白(MAP)。缺乏MAPS(MAPS−/−)的小鼠会出现粗线期停滞和精母细胞死亡，导致男性不育，而女性的生育能力不受影响。有趣的是，青春期MAPs−/−精母细胞停滞在粗线期的早期，伴随着DNA双链断裂修复、交叉形成和XY小体形成的缺陷。相反，成年MAPS−/−精母细胞只表现出部分缺陷的交叉，但从粗线期早期到粗线期中晚期的进展延迟或失败，导致细胞死亡。此外，我们报告了青春期和成年MAP−/−粗线期精母细胞中常染色体和XY染色体显著的转录异常，包括减数分裂失败的性染色体失活。进一步的实验表明，MAPs在体外的过度表达显著降低了细胞蛋白质的泛素化水平。相反，在MAP−/−粗线期细胞中，蛋白质泛素化显著增加，这可能是粗线期细胞基因表达大规模中断的原因。因此，MAP是雄性小鼠肥厚病进展所必需的一种蛋白质，可能在一般哺乳动物中也是如此。
During meiosis prophase I in mammals, a series of events occur, such as homologous recombination, DSB repair, crossover formation, XY body formation, and meiotic sex chromosome inactivation (MSCI). We report here that a male pachynema-specific (MAPS) protein is essential for prophase I progression in mouse spermatocytes. Maps knockout causes the demise of pachytene spermatocytes throughout early to mid- and late pachynema, resulting in male but not female infertility. Moreover, protein ubiquitination was dramatically increased in Maps−/− pachytene spermatocytes, likely contributing to the dysregulated global gene expression, including failed MSCI. In summary, MAPS is an indispensable protein for male fertility. Meiosis is a specialized cell division that creates haploid germ cells from diploid progenitors. Through differential RNA expression analyses, we previously identified a number of mouse genes that were dramatically elevated in spermatocytes, relative to their very low expression in spermatogonia and somatic organs. Here, we investigated in detail 1700102P08Rik, one of these genes, and independently conclude that it encodes a male germline-specific protein, in agreement with a recent report. We demonstrated that it is essential for pachynema progression in spermatocytes and named it male pachynema-specific (MAPS) protein. Mice lacking Maps (Maps−/−) suffered from pachytene arrest and spermatocyte death, leading to male infertility, whereas female fertility was not affected. Interestingly, pubertal Maps−/− spermatocytes were arrested at early pachytene stage, accompanied by defects in DNA double-strand break (DSB) repair, crossover formation, and XY body formation. In contrast, adult Maps−/− spermatocytes only exhibited partially defective crossover but nonetheless were delayed or failed in progression from early to mid- and late pachytene stage, resulting in cell death. Furthermore, we report a significant transcriptional dysregulation in autosomes and XY chromosomes in both pubertal and adult Maps−/− pachytene spermatocytes, including failed meiotic sex chromosome inactivation (MSCI). Further experiments revealed that MAPS overexpression in vitro dramatically decreased the ubiquitination levels of cellular proteins. Conversely, in Maps−/− pachytene cells, protein ubiquitination was dramatically increased, likely contributing to the large-scale disruption in gene expression in pachytene cells. Thus, MAPS is a protein essential for pachynema progression in male mice, possibly in mammals in general.
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