Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis.
Sperm Associated Antigen 6 (SPAG6) Regulates Fibroblast Cell Growth, Morphology, Migration and Ciliogenesis.
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精子相关抗原 6 (SPAG6) 调节成纤维细胞生长、形态、迁移和纤毛发生
DOI：
10.1038/srep16506
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发表时间：
2015-11-20
影响因子：
4.6
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Li W;Mukherjee A;Wu J;Zhang L;Teves ME;Li H;Nambiar S;Henderson SC;Horwitz AR;Strauss JF III;Fang X;Zhang Z
哺乳动物Spag 6是衣原体PF 16的直向同源物，其编码定位于轴丝中央装置中的蛋白并调节鞭毛/纤毛运动。大多数Spag 6缺陷小鼠的体型都比同窝出生的小鼠小。由于SPAG 6修饰微管，我们假设SPAG 6除了调节鞭毛/纤毛运动外，还具有与微管功能相关的其他作用。从Spag 6缺陷型和野生型胚胎中分离小鼠胚胎成纤维细胞（MEFs）用于这些研究。原发性和immortalizedSpag 6缺陷型MEFs的增殖速度比野生型MEFs慢得多，它们具有更大的表面积。Spag 6缺陷的MEFs中SPag 6的重新表达挽救了异常的细胞形态学。与野生型MEFs相比，Spag 6缺陷的MEFs的运动性更差，如趋化性分析和伤口愈合试验所示; Spag 6缺陷的MEFs还显示与非极化的F-actin分布相关的粘附性降低。在Spag 6缺陷的MEF培养物中观察到多个中心体。与野生型MEFs相比，具有初级纤毛的细胞的百分比显著降低，并且一些Spag 6缺陷的MEFs产生多个纤毛。此外，SPAG 6选择性地增加乙酰化微管蛋白（微管稳定性标志物）的表达。Spag 6缺陷的MEFs对微管稳定剂紫杉醇更敏感。我们的研究揭示了SPAG 6在调节细胞形态、增殖、迁移和纤毛发生中的新作用。
MammalianSpag6is the orthologue of ChlamydomonasPF16, which encodes a protein localized in the axoneme central apparatus and regulates flagella/cilia motility. MostSpag6-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 fromSpag6-deficient and wild-type embryos for these studies. Both primary and immortalizedSpag6-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 theSpag6-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 theSpag6-deficient MEF cultures. The percentage of cells with primary cilia was significantly reduced compared to the wild-type MEFs and someSpag6-deficient MEFs developed multiple cilia. Furthermore, SPAG6 selectively increased expression of acetylated tubulin, a microtubule stability marker. TheSpag6-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.