Testis-specific serine protease PRSS54 regulates acrosomal granule localization and sperm head morphogenesis in mice

Testis-specific serine protease PRSS54 regulates acrosomal granule localization and sperm head morphogenesis in mice
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睾丸特异性丝氨酸蛋白酶 PRSS54 调节小鼠顶体颗粒定位和精子头形态发生

DOI:
10.1093/biolre/ioac146
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发表时间:
2022-07
影响因子:
3.6
通讯作者:
Zhugang Wang
Zhugang Wang
中科院分区:
生物学2区
文献类型:
--
作者:
Chunling Shen;Wenfeng Xiong;Chaojie Li;Haoyang Ge;Yan Shen;Lingyun Tang;Hongxin Zhang;Shunyuan Lu;Jian Fei;Zhugang Wang

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摘要丝氨酸蛋白酶(PRSS)约占蛋白酶的三分之一,其中许多是睾丸特异性蛋白酶,在精子发育和男性生殖过程中起着重要作用。PRSS 54是小鼠和人类睾丸特异性的PRSS之一,但其生理功能在很大程度上仍不清楚。在本研究中,我们详细证明,PRSS 54不仅存在于睾丸,但也在成熟的精子,表现出的蛋白质大小的变化,从50 kDa的睾丸到42 kDa的精子。PRSS 54基因缺失可导致小鼠雄性不育、顶体畸形、精子穿透缺陷,而PrSS 54转基因可挽救雄性不育和顶体畸形的表型。透射电子显微镜的超微结构分析进一步揭示了Prss 54-/-精子细胞在精子发生过程中的各种形态学异常,包括顶体中未融合的空泡、顶体颗粒的分离和偏心定位以及核的不对称伸长。PRSS 54的亚细胞定位显示,在精子顶体发生的早期,它首先出现在顶体颗粒中,然后沿着顶体内膜延伸,最后出现在成熟精子的顶体区域。PRSS 54与顶体蛋白ZPBP 1、ZPBP 2、ACRBP和ZP 3R相互作用,PRSS 54的缺失影响这些蛋白在睾丸和精子中的分布,尽管它们的蛋白水平在很大程度上不受影响。此外,Prss 54-/-精子对顶体反应诱导剂更敏感。这些数据表明PRSS 54是一种顶体蛋白,在调节顶体生物发生、精子功能和男性生育力方面起重要作用。图形摘要
Abstract Serine proteases (PRSS) constitute nearly one-third of all proteases, and many of them have been identified to be testis-specific and play significant roles during sperm development and male reproduction. PRSS54 is one of the testis-specific PRSS in mouse and human but its physiological function remains largely unclear. In the present study, we demonstrate in detail that PRSS54 exists not only in testis but also in mature sperm, exhibiting a change in protein size from 50 kDa in testis to 42 kDa in sperm. Loss of PRSS54 in mice results in male subfertility, acrosome deformation, defective sperm–zona penetration, and phenotypes of male subfertility and acrosome deformation can be rescued by Prss54 transgene. Ultrastructure analyses by transmission electronic microscopy further reveal various morphological abnormalities of Prss54–/– spermatids during spermiogenesis, including unfused vacuoles in acrosome, detachment and eccentrical localization of the acrosomal granules, and asymmetrical elongation of the nucleus. Subcellular localization of PRSS54 display that it appears in the acrosomal granule at the early phase of acrosome biogenesis, then extends along the inner acrosomal membrane, and ultimately presents in the acrosome region of the mature sperm. PRSS54 interacts with acrosomal proteins ZPBP1, ZPBP2, ACRBP, and ZP3R, and loss of PRSS54 affects the distribution of these proteins in testis and sperm, although their protein levels are largely unaffected. Moreover, Prss54–/– sperm are more sensitive to acrosome reaction inducers. Summary Sentence These data indicate that PRSS54 is an acrosomal protein and plays an important role in regulating acrosome biogenesis, sperm function, and male fertility. Graphical Abstract
DOI: 10.1016/s0015-0282(16)48918-1
发表时间: 1985-10
影响因子: 6.7
作者:
P. Quinn;J. Kerin;G. Warnes
通讯作者: P. Quinn;J. Kerin;G. Warnes
DOI: 10.1073/pnas.1635054100
发表时间: 2003-10-14
影响因子: 11.1
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DOI: 10.1093/biolre/ioz158
发表时间: 2020-01-01
影响因子: 3.6
作者:
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通讯作者: Garcia, Thomas X.
DOI: 10.1093/emboj/20.4.694
发表时间: 2001-02-15
期刊: EMBO JOURNAL
影响因子: 11.4
作者:
Rossi, D;Cozzio, A;Weissmann, C
通讯作者: Weissmann, C
DOI: 10.1095/biolreprod.109.076273
发表时间: 2009-11-01
影响因子: 3.6
作者:
Netzel-Arnett, Sarah;Bugge, Thomas H.;Antalis, Toni M.
通讯作者: Antalis, Toni M.