PTMs and MAPs are known to regulate Microtubule dynamicity in somatic cells. Reported literature on modulation of α tubulin acetyl transferase (αTAT1) and Histone deacetylase 6 (HDAC6) in animal models and cell lines illustrates disparity in correlating tubulin acetylation status with stability of MT. Our earlier studies showed reduced acetyl tubulin in sperm of asthenozoospermic individuals. Our studies on rat sperm showed that on inhibition of HDAC6 activity although tubulin acetylation increased, sperm motility was reduced. Studies were therefore undertaken to investigate the influence of tubulin acetylation/deacetylation on MT dynamicity in sperm flagella using rat- and human sperm. Our data on rat sperm revealed that HDAC6 specific inhibitor Tubastatin A (T) inhibited sperm motility and neutralized the depolymerizing and motility debilitating effect of Nocodazole. The effect on polymerization was further confirmed in vitro using pure MT and recHDAC6. Also polymerized axoneme was less in sperm of asthenozoosperm compared to normozoosperm. Deacetylase activity was reduced in sperm- lysates and axonemes exposed to T and N+T but not in axonemes of sperm treated similarly suggesting that HDAC6 is associated with sperm axonemes or MT. Deacetylase activity was less in asthenozoosperm. Intriguingly, the expression of MDP3 physiologically known to bind to HDAC6 and inhibit its deacetylase activity, remained unchanged. However expression of acetyl α tubulin, HDAC6 and microtubule stabilizing protein SAXO1 was less in asthenozoosperm. These observations suggest that MAPs and threshold levels of MT acetylation/deacetylation are important for MT dynamicity in sperm and may play a role in regulating sperm motility.

中文翻译：

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乙酰化/去乙酰化和微管相关蛋白会影响鞭毛的轴突稳定性和精子活力。

已知PTM和MAP调节体细胞中的微管动态。在动物模型和细胞系中有关α微管蛋白乙酰基转移酶（αTAT1）和组蛋白脱乙酰基酶6（HDAC6）调节的报道文献表明，微管蛋白乙酰化状态与MT稳定性之间存在差异。我们较早的研究表明，弱精子症患者精子中的乙酰微管蛋白减少。我们对大鼠精子的研究表明，尽管微管蛋白乙酰化增加，但对HDAC6活性的抑制作用使精子运动力降低。因此，进行了研究，以研究使用大鼠和人类精子的微管蛋白乙酰化/脱乙酰化对鞭毛中MT动态的影响。我们在大鼠精子上的数据显示，HDAC6特异性抑制剂Tubastatin A（T）抑制精子运动，并中和了Nocodazole的解聚和运动衰弱作用。使用纯MT和recHDAC6在体外进一步证实了对聚合的影响。同样，弱精子精子中聚合的轴突素比正常精子中的少。暴露于T和N + T的精液和轴突中的脱乙酰基酶活性降低，但经过类似处理的精子轴突中的脱乙酰基酶活性并未降低，这表明HDAC6与精子轴突或MT相关。弱精子中的脱乙酰酶活性较低。有趣的是，生理上已知与HDAC6结合并抑制其脱乙酰酶活性的MDP3的表达保持不变。然而，弱精子症中乙酰α微管蛋白，HDAC6和微管稳定蛋白SAXO1的表达较少。