AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function.
AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function.
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DOI：
10.1016/j.ajpath.2015.10.007
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Deepak Venkatesh;D. Mruk;J. Herter;X. Cullere;K. Chojnacka;C. Cheng;T. Mayadas
中科院分区：
文献类型：
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作者：
Deepak Venkatesh;D. Mruk;J. Herter;X. Cullere;K. Chojnacka;C. Cheng;T. Mayadas
在相邻的支持细胞之间形成的血-睾丸屏障(BTB)经历了广泛的重塑，以促进纤毛虫前期精母细胞从生精小管的基底部到顶室的屏障的运输，从而进一步发育和成熟为精子。肌动蛋白细胞骨架在这一过程中发挥着独特的结构和支持作用，但对微管及其调节因子在BTB重组中的作用知之甚少。CAMP反应支架蛋白AKAP9的大亚型调节微管的动力学和高尔基体的成核。我们发现，在小鼠青春期BTB最初形成后，Akap9的有条件缺失会导致不育。Akap9缺失会导致支持细胞微管组织的显著变化，并导致屏障完整性的丧失，尽管F-肌动蛋白和BTB紧密连接蛋白相对完整，但更多地位于顶部。这些变化伴随着由于减数分裂受阻而导致的单倍体精子细胞的丧失。然而，在Akap9基因缺失的老年小鼠中，这种屏障逐渐重新封闭，这与生殖细胞凋亡的减少和减数分裂的发生率更高有关。然而，精子发生仍然存在缺陷，这表明AKAP9在这一过程中扮演了更多的角色。综上所述，我们的数据表明，AKAP9以及由此推断的微管网络的调节对于BTB的功能和随后的精子发生过程中生殖细胞的发育至关重要。
The blood-testis barrier (BTB), formed between adjacent Sertoli cells, undergoes extensive remodeling to facilitate the transport of preleptotene spermatocytes across the barrier from the basal to apical compartments of the seminiferous tubules for further development and maturation into spermatozoa. The actin cytoskeleton serves unique structural and supporting roles in this process, but little is known about the role of microtubules and their regulators during BTB restructuring. The large isoform of the cAMP-responsive scaffold protein AKAP9 regulates microtubule dynamics and nucleation at the Golgi. We found that conditional deletion ofAkap9in mice after the initial formation of the BTB at puberty leads to infertility.Akap9deletion results in marked alterations in the organization of microtubules in Sertoli cells and a loss of barrier integrity despite a relatively intact, albeit more apically localized F-actin and BTB tight junctional proteins. These changes are accompanied by a loss of haploid spermatids due to impeded meiosis. The barrier, however, progressively reseals in olderAkap9null mice, which correlates with a reduction in germ cell apoptosis and a greater incidence of meiosis. However, spermiogenesis remains defective, suggesting additional roles for AKAP9 in this process. Together, our data suggest that AKAP9 and, by inference, the regulation of the microtubule network are critical for BTB function and subsequent germ cell development during spermatogenesis.