Essential role for SUN5 in anchoring sperm head to the tail

Essential role for SUN5 in anchoring sperm head to the tail
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SUN5 在将精子头部固定到尾部方面发挥重要作用

DOI:
10.7554/elife.28199.001
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发表时间:
2017-09-25
期刊:
影响因子:
7.7
通讯作者:
Li, Wei
Li, Wei
中科院分区:
生物学1区
文献类型:
--
作者:
Shang, Yongliang;Zhu, Fuxi;Li, Wei

文献摘要

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据报道,含SUN(Sad1和UNC84结构域)结构域的蛋白质定位于核膜,在核动力学中发挥不同作用。SUN5是SUN家族的新成员,其功能鲜为人知。在此,我们构建了Sun5基因敲除(Sun5 - / - )小鼠,发现雄性小鼠不育。大多数Sun5基因缺失的精子呈现出类圆头精子症的表型,但实际上它们是无头精子。进一步研究表明,SUN5定位于精子颈部,将精子头部与尾部相连,在精子细胞伸长过程中,若无功能性的SUN5,精子头尾连接装置会从细胞核上脱离。最后,我们发现通过对雄性小鼠和患者的Sun5突变精子头部进行胞质内注射,可获得健康的杂合子后代。我们的研究揭示了SUN5在连接精子头部与尾部中的关键作用,并为治疗这类无头精子相关的男性不育症提供了一种有前景的方法。
SUN (Sad1 and UNC84 domain containing)-domain proteins are reported to reside on the nuclear membrane playing distinct roles in nuclear dynamics. SUN5 is a new member of the SUN family, with little knowledge regarding its function. Here, we generated Sun5(-/-) mice and found that male mice were infertile. Most Sun5-null spermatozoa displayed a globozoospermia-like phenotype but they were actually acephalic spermatozoa. Additional studies revealed that SUN5 was located in the neck of the spermatozoa, anchoring sperm head to the tail, and without functional SUN5 the sperm head to tail coupling apparatus was detached from nucleus during spermatid elongation. Finally, we found that healthy heterozygous offspring could be obtained via intracytoplasmic injection of Sun5-mutated sperm heads for both male mice and patients. Our studies reveal the essential role of SUN5 in anchoring sperm head to the tail and provide a promising way to treat this kind of acephalic spermatozoa-associated male infertility.