LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.
LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.
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DOI：
10.1371/journal.pgen.1005090
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发表时间：
2015-03
期刊：
影响因子：
4.5
通讯作者：
O'Bryan MK
中科院分区：
文献类型：
--
作者：
Liu Y;DeBoer K;de Kretser DM;O'Donnell L;O'Connor AE;Merriner DJ;Okuda H;Whittle B;Jans DA;Efthymiadis A;McLachlan RI;Ormandy CJ;Goodnow CC;Jamsai D;O'Bryan MK
男性不育影响至少5%的育龄男性。最常见的病理是精子数量减少和精子形状和运动异常的复杂表现，称为少弱性异卵精子症（OAT）。对于大多数OAT男性来说，无法提供精确的诊断。在这里，我们证明了富含亮氨酸的重复序列和含有鸟苷酸激酶结构域的异构体1 （LRGUK-1）是精子组装的多个方面所必需的，包括顶体附着、精子头部形成和轴突生长的起始，以形成精子尾部的核心。具体来说，LRGUK-1对于基底体与质膜的附着、亚远端附属物的适当形成、轴突微管的延伸以及微管在颌内的运动和组织都是必需的。Manchette功能障碍导致精子头部形状异常。其中一些功能可以通过LRGUK-1的结合伙伴HOOK2来实现。总的来说，这些数据表明LRGUK-1是男性生殖系微管结构的主要决定因素。在西方社会，男性不育影响六分之一的夫妇，其中大约一半是男性因素失调的结果。男性不育症最常见的临床表现是精子数量、形状和活力异常的复杂混合体，称为少弱异卵精子症（OAT）。为了确定OAT的起源，我们分析了富含亮氨酸重复序列和鸟苷酸激酶结构域1 （LRGUK-1）功能障碍的小鼠模型。本研究表明，LRGUK在单倍体生殖细胞成熟（精子发生）过程中动态重新分布，并且LRGUK-1的功能在精子中心粒和尾部发育以及精子头部形成的多个方面都是必需的。此外，我们已经确定HOOK2是一个新的LRGUK-1结合伙伴，从而提高了与HOOK2合作实现LRGUK-1功能的几个方面的可能性。
Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line. Male infertility affects one in six couples in western societies and approximately half of these are the result of male factor disorders. The most common clinical presentation for male infertility is a complex mixture of abnormal sperm output, shape and motility referred to as oligoasthenoteratozoospermia (OAT). In an effort to define an origin of OAT we have analysed a mouse model of leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) dysfunction. Herein we show that LRGUK dynamically redistributes during the process of haploid germ cell maturation (spermiogenesis) and that LRGUK-1 function is required for multiple aspects of sperm centriole and tail development and sperm head shaping. Further, we have identified HOOK2 as a novel LRGUK-1 binding partner, thus raising the possibility that several aspects of LRGUK-1 function are achieved in partnership with HOOK2.
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