JMY expression by Sertoli cells contributes to mediating spermatogenesis in mice
JMY expression by Sertoli cells contributes to mediating spermatogenesis in mice
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支持细胞表达 JMY 有助于介导小鼠精子发生
DOI：
10.1111/febs.15328
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发表时间：
2020-04-23
期刊：
影响因子：
5.4
通讯作者：
Ding, Zhide
中科院分区：
文献类型：
--
作者：
Liu, Yue;Fan, Jiaying;Ding, Zhide
支持细胞对于生精上皮中的精子发生至关重要，因为其肌动蛋白细胞骨架支持囊泡运输、细胞连接形成、蛋白质锚定以及精子释放。在此，我们表明一种连接介导和肌动蛋白调节蛋白（JMY）通过重塑支持细胞连接完整性来影响血 - 组织屏障（BTB）功能，并且它还有助于控制内吞囊泡运输。这些功能对于维持精子生育能力至关重要，因为支持细胞特异性Jmy功能缺失会导致小鼠雄性生育力下降。具体而言，这些小鼠具有以下情况：（a）生精小管中BTB完整性和精子细胞黏附受损；（b）精子结构畸形发生率高；（c）精子数量减少且精子活力差。此外，细胞骨架完整性以及内吞囊泡运输均受到损害。这些影响破坏了连接蛋白的循环利用，并降低了支持细胞BTB连接的完整性。此外，JMY与肌动蛋白结合蛋白候选物α - 辅肌动蛋白1以及含 sorbin和SH3结构域的蛋白2的相互作用与JMY活性相关，进而与肌动蛋白细胞骨架组织相关。总之，JMY通过调节支持细胞中肌动蛋白丝的组织和内吞囊泡运输来影响精子发生的调控。
Sertoli cells are crucial for spermatogenesis in the seminiferous epithelium because their actin cytoskeleton supports vesicular transport, cell junction formation, protein anchoring, and spermiation. Here, we show that a junction-mediating and actin-regulatory protein (JMY) affects the blood-tissue barrier (BTB) function through remodeling of the Sertoli cell junctional integrity and it also contributes to controlling endocytic vesicle trafficking. These functions are critical for the maintenance of sperm fertility since loss of Sertoli cell-specific Jmy function induced male subfertility in mice. Specifically, these mice have (a) impaired BTB integrity and spermatid adhesion in the seminiferous tubules; (b) high incidence of sperm structural deformity; and (c) reduced sperm count and poor sperm motility. Moreover, the cytoskeletal integrity was compromised along with endocytic vesicular trafficking. These effects impaired junctional protein recycling and reduced Sertoli cell BTB junctional integrity. In addition, JMY interaction with actin-binding protein candidates alpha-actinin1 and sorbin and SH3 domain containing protein 2 was related to JMY activity, and in turn, actin cytoskeletal organization. In summary, JMY affects the control of spermatogenesis through the regulation of actin filament organization and endocytic vesicle trafficking in Sertoli cells.