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2016年1月19日讯/生物谷BIOON/弗吉尼亚联邦大学医学院的研究人员最新发现，精子相关抗原6(SPAG6) 有了某些新的功能， 以前这种基因被认为只对纤毛的能动性有重要作用。该基因的缺陷与男性不育相关，尽管新的发现可能会对某些癌症的诊断和治疗有影响。
“精子抗原6调节成纤维细胞的生长、形态、迁移和纤毛发生。”该研究发表在11月的《Scientific Reports》杂志上。
“我发现了一个新的复杂的基因组，它发挥着多重作用，包括对精子形成、听力和免疫突触的形成都有作用。”Zhibing Zhang博士说。“我的假设基于微管的运输系统是非常复杂的。”
微管是非常厚的，较强的螺旋蛋白质可帮助定义真核细胞的细胞结构和运动，这是我们生命的基本单位。SPAG6基因似乎在整装微管从而使其结构更强。当SPAG6缺乏时微管就非常的脆弱。
Zhang博士因为他的实验室项目对该基因增加的功能有了进一步了解 ，SPAG6缺乏的小鼠，显示出一些与纤毛蠕动减少无关的特征。“当我开始观察小鼠的时候，我意识到这种机制不能解释所有的表型。”Zhang说。表型是可以观察到的特征，与其野生型的同窝出生的小鼠相比，SPAG6缺乏的小鼠都是聋子，体型较小，并且大多数死于脑积水，伴随着异常脑脊液积累到大脑。
除了增加细胞功能， SPAG 6的表达似乎与对紫杉醇敏感性有关，微管稳定性药物用于治疗肺癌、乳腺癌和卵巢癌等。
先前的研究已经表明SPAG6在人类体内的表达会在某些恶性肿瘤中有所增加。“我们认为这种基因的超表达是为什么有些癌症抵抗微管靶向药物（如紫杉醇）的其中一个原因。”Zhang说。他发现SPAG6缺乏的小鼠胚胎成纤维细胞对紫杉醇更敏感，他最近的研究表明，减少SPAG6在卵巢癌细胞中的表达可增加对紫杉醇敏感性。“这些研究强烈表明SPAG6是一种新型的治疗某些癌症的靶向药物，尤其是抗紫杉醇的癌症药物。”
（基因宝jiyinbao.com）
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doi:10.1038/srep16506
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Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis
Wei Li, Abir Mukherjee, Jinhua Wu, Ling Zhang, Maria E. Teves, Hongfei Li, Shanti Nambiar, Scott C. Henderson, Alan R. Horwitz, Jerome F. Strauss III, Xianjun Fang & Zhibing Zhang
Mammalian Spag6 is the orthologue of Chlamydomonas PF16, which encodes a protein localized in the axoneme central apparatus, and regulates flagella/cilia motility. Most Spag6-deficient mice are smaller in size than their littermates. Because SPAG6 decorates microtubules, we hypothesized that SPAG6 has other roles related to microtubule function besides regulating flagellar/cilia motility. Mouse embryonic fibroblasts (MEFs) were isolated from Spag6-deficient and wild-type embryos for these studies. Both primary and immortalized Spag6-deficient MEFs proliferated at a much slower rate than the wild-type MEFs, and they had a larger surface area. Re-expression of SPAG6 in the Spag6-deficient MEFs rescued the abnormal cell morphology. Spag6-deficient MEFs were less motile than wild-type MEFs, as shown by both chemotactic analysis and wound-healing assays. Spag6-deficient MEFs also showed reduced adhesion associated with a non-polarized F-actin distribution. Multiple centrosomes were observed in the Spag6-deficient MEF cultures. The percentage of cells with primary cilia was significantly reduced compared to the wild-type MEFs, and some Spag6-deficient MEFs developed multiple cilia. Furthermore, SPAG6 selectively increased expression of acetylated tubulin, a microtubule stability marker. The Spag6-deficient MEFs were more sensitive to paclitaxel, a microtubule stabilizer. Our studies reveal new roles for SPAG6 in modulation of cell morphology, proliferation, migration, and ciliogenesis.