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基因突变导致精子尾部组成异常,从而引起男性不育。

Genetic mutation of results in male infertility due to abnormal sperm tail composition.

机构信息

https://ror.org/01ej9dk98 School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, The University of Melbourne, Parkville, Australia

https://ror.org/01ej9dk98 School of BioSciences and Bio21 Molecular Sciences and Biotechnology Institute, The University of Melbourne, Parkville, Australia.

出版信息

Life Sci Alliance. 2024 Apr 3;7(6). doi: 10.26508/lsa.202302452. Print 2024 Jun.

DOI:10.26508/lsa.202302452
PMID:38570187
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10992998/
Abstract

The transition zone is a specialised gate at the base of cilia/flagella, which separates the ciliary compartment from the cytoplasm and strictly regulates protein entry. We identified a potential new regulator of the male germ cell transition zone, CEP76. We demonstrated that CEP76 was involved in the selective entry and incorporation of key proteins required for sperm function and fertility into the ciliary compartment and ultimately the sperm tail. In the mutant, sperm tails were shorter and immotile as a consequence of deficits in essential sperm motility proteins including DNAH2 and AKAP4, which accumulated at the sperm neck in the mutant. Severe annulus, fibrous sheath, and outer dense fibre abnormalities were also detected in sperm lacking CEP76. Finally, we identified that CEP76 dictates annulus positioning and structure. This study suggests CEP76 as a male germ cell transition zone protein and adds further evidence to the hypothesis that the spermatid transition zone and annulus are part of the same functional structure.

摘要

过渡区是纤毛/鞭毛底部的一个特殊门,将纤毛隔室与细胞质隔开,并严格调节蛋白质的进入。我们鉴定了一个雄性生殖细胞过渡区的潜在新调节剂,CEP76。我们证明 CEP76 参与了选择性进入和整合关键蛋白质,这些蛋白质对于精子功能和生育能力是必需的,进入纤毛隔室,并最终进入精子尾部。在突变体中,由于包括 DNAH2 和 AKAP4 在内的关键精子运动蛋白的缺乏,精子尾部更短且不动,这些蛋白在突变体中积累在精子颈部。还在缺乏 CEP76 的精子中检测到严重的环、纤维鞘和外致密纤维异常。最后,我们确定 CEP76 决定了环的位置和结构。本研究将 CEP76 鉴定为雄性生殖细胞过渡区蛋白,并为精子过渡区和环是同一功能结构的一部分这一假说提供了更多证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/bfcfe059f364/LSA-2023-02452_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/b78bcdcb392c/LSA-2023-02452_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/b3e6a2d5affa/LSA-2023-02452_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/405407fb9775/LSA-2023-02452_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/4a84f0ed3127/LSA-2023-02452_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/12b476bdb8d7/LSA-2023-02452_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/d2267afad29f/LSA-2023-02452_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/6ebc803a18cc/LSA-2023-02452_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/166de5cf09df/LSA-2023-02452_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/6b45f6c376ae/LSA-2023-02452_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/bfcfe059f364/LSA-2023-02452_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/b78bcdcb392c/LSA-2023-02452_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/b3e6a2d5affa/LSA-2023-02452_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/405407fb9775/LSA-2023-02452_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/4a84f0ed3127/LSA-2023-02452_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/12b476bdb8d7/LSA-2023-02452_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/d2267afad29f/LSA-2023-02452_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/6ebc803a18cc/LSA-2023-02452_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/166de5cf09df/LSA-2023-02452_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/6b45f6c376ae/LSA-2023-02452_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4a2/10992998/bfcfe059f364/LSA-2023-02452_Fig5.jpg

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2
Ciliary transition zone proteins coordinate ciliary protein composition and ectosome shedding.纤毛过渡区蛋白协调纤毛蛋白组成和胞外小体脱落。
Nat Commun. 2022 Jul 9;13(1):3997. doi: 10.1038/s41467-022-31751-0.
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Structural Biology of Cilia and Intraflagellar Transport.纤毛与鞭毛内运输的结构生物学
Annu Rev Cell Dev Biol. 2022 Oct 6;38:103-123. doi: 10.1146/annurev-cellbio-120219-034238. Epub 2022 Jun 29.
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KATNB1 is a master regulator of multiple katanin enzymes in male meiosis and haploid germ cell development.KATNB1 是雄性减数分裂和单倍体生殖细胞发育中多种katanin 酶的主要调节因子。
Development. 2021 Dec 15;148(24). doi: 10.1242/dev.199922.
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A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene-disease relationships.一项关于人类男性不育症已验证的单基因病因的系统综述:2020 年更新及对新兴基因-疾病关系的讨论。
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