LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice

LRRC23 is a conserved component of the radial spoke that is necessary for sperm motility and male fertility in mice
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LRRC23 是径向辐条的保守成分,对于小鼠精子活力和雄性生育能力是必需的

DOI:
10.1101/2021.06.01.446532
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发表时间:
2021-06
影响因子:
4
通讯作者:
Liu M
Liu M
中科院分区:
生物学2区
文献类型:
--
作者:
Zhang X;Sun J;Lu Y;Zhang J;Shimada K;Noda T;Zhao S;Koyano T;Matsuyama M;Zhou S;Wu J;Ikawa M;Liu M

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纤毛和鞭毛是通过包括动力蛋白臂、径向辐条(RS)、微管和动力蛋白调节复合物(DRC)的结构的协调相互作用来实现受控运动功能的古老结构。RSs通过介导动力蛋白和单线态微管中心对(CP)之间的信号转导促进这些细胞器的跳动运动。从衣原体轴丝中分离的RS复合物能够检测23种不同的蛋白质(RSP 1 -23),RSP 13、RSP 15、RSP 18、RSP 19和RSP 21的作用仍然知之甚少。在此,我们表明,Lrrc 23是一个进化上保守的睾丸丰富的基因编码的RSP 15同源物在小鼠中。通过免疫电镜,我们证明LRRC 23定位于小鼠精子鞭毛内的RS复合物。我们进一步发现LRRC 23能够与RSHP 9和RSPH 3A/B相互作用。敲除Lrrc 23导致小鼠精子RS解体和运动受损,而纤毛跳动不受这种蛋白质的损失。缺乏LRRC 23的精子不能有效地通过子宫输卵管连接处,并表现出有缺陷的精子穿透。总之,这些数据表明,LRRC 23是一个关键的调节器,支持哺乳动物精子鞭毛内的RS复合物的完整性,而它是纤毛。作者摘要
Cilia and flagella are ancient structures that achieve controlled motor functions through the coordinated interaction of structures including dynein arms, radial spokes (RSs), microtubules, and the dynein regulatory complex (DRC). RSs facilitate the beating motion of these organelles by mediating signal transduction between dyneins and a central pair (CP) of singlet microtubules. RS complex isolation from Chlamydomonas axonemes enabled the detection of 23 different proteins (RSP1-23), with the roles of RSP13, RSP15, RSP18, RSP19, and RSP21 remained poorly understood. Herein, we show that Lrrc23 is an evolutionarily conserved testis-enriched gene encoding an RSP15 homolog in mice. Through immunoelectron microscopy, we demonstrate that LRRC23 localizes to the RS complex within murine sperm flagella. We further found that LRRC23 was able to interact with RSHP9 and RSPH3A/B. The knockout of Lrrc23 resulted in RS disorganization and impaired motility in murine spermatozoa, whereas the ciliary beating was unaffected by the loss of this protein. Spermatozoa lacking LRRC23 were unable to efficiently pass through the uterotubal junction and exhibited defective zona penetration. Together these data indicate that LRRC23 is a key regulator underpinning the integrity of RS complex within the flagella of mammalian spermatozoa, whereas it is dispensable in cilia. Author summary
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