Department of Internal Medicine I, Regensburg University Hospital, Regensburg, Germany.
Institute of Genetics, University of Regensburg, Regensburg, Germany.
J Physiol Biochem. 2018 Nov;74(4):511-521. doi: 10.1007/s13105-018-0645-x. Epub 2018 Jul 22.
The scaffold protein alpha-syntrophin (SNTA) is a component of the dystrophin glycoprotein complex and has been comprehensively studied in skeletal muscle and adipocytes. SNTA is further expressed in the liver where its biological role remains unclear. Unpublished data from our group suggested that SNTA deficiency is associated with altered tubulin alpha 8 (TUBA8) levels in fat. TUBA8 is highly expressed in different cell lines including hepatoma cells, and here we analyzed whether SNTA has a role herein. In Hepa1-6 cells, TUBA8 protein levels were increased upon SNTA knock down and were reduced upon overexpression of SNTA. This regulation was not identified when analyzing mRNA expression. In the liver of SNTA-deficient mice, TUBA8 protein was higher compared to the respective wild-type controls while RNA expression was even suppressed. Using the HaloTag platform, TUBA8 was found to form a complex with SNTA in Hepa1-6 cells. In the hepatic stellate cell line LX-2, the lack or overexpression of SNTA did, however, not change TUBA8 protein expression. SNTA and TUBA8 are described to regulate cell proliferation. Yet, knock down of SNTA did neither affect proliferation nor viability of Hepa1-6 cells. The present study shows that SNTA protein levels are inversely related to TUBA8 protein expression in the hepatocyte cell line Hepa1-6.
支架蛋白α-突触核蛋白 (SNTA) 是肌营养不良糖蛋白复合物的组成部分,在骨骼肌和脂肪细胞中得到了广泛研究。SNTA 在肝脏中进一步表达,但其生物学功能尚不清楚。我们小组的未发表数据表明,SNTA 缺乏与脂肪中微管蛋白 alpha 8 (TUBA8) 水平的改变有关。TUBA8 在不同的细胞系中高度表达,包括肝癌细胞,在这里我们分析了 SNTA 是否在此起作用。在 Hepa1-6 细胞中,SNTA 敲低后 TUBA8 蛋白水平增加,SNTA 过表达后 TUBA8 蛋白水平降低。当分析 mRNA 表达时,没有发现这种调节。在 SNTA 缺陷型小鼠的肝脏中,TUBA8 蛋白水平高于相应的野生型对照,而 RNA 表达甚至受到抑制。使用 HaloTag 平台,在 Hepa1-6 细胞中发现 TUBA8 与 SNTA 形成复合物。然而,在肝星状细胞系 LX-2 中,SNTA 的缺失或过表达并未改变 TUBA8 蛋白表达。SNTA 和 TUBA8 被描述为调节细胞增殖。然而,SNTA 的敲低既不影响 Hepa1-6 细胞的增殖也不影响其活力。本研究表明,在 Hepa1-6 肝细胞系中,SNTA 蛋白水平与 TUBA8 蛋白表达呈负相关。