Song Jonathan, Carson John H, Barbarese Elisa, Li Fang-Yuan, Duncan Ian D
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
Mol Cell Neurosci. 2003 Dec;24(4):926-38. doi: 10.1016/s1044-7431(03)00254-9.
The results presented here identify a new RNA trafficking phenotype in taiep oligodendrocytes that increases the frequency of reversals and restricts the extent of transport of RNA containing the A2RE transport signal from MBP mRNA. The taiep rat is a myelin mutant characterized by excessive accumulation of microtubules in oligodendrocytes and myelin deficiency in the central nervous system. The taiep RNA trafficking is developmentally correlated with the microtubule accumulation in oligodendrocytes and can be partially suppressed by reducing microtubule density with nocodazole or inhibiting dynein activity by coinjecting anti-dynein antibodies. These results suggest that RNA trafficking in taiep oligodendrocytes is inhibited by enhanced dynein activity that neutralizes or lessens the normal overriding power of the plus-end directed motor kinesin. Altered orientation of microtubules in oligodendrocyte fine processes and a physical barrier created by densely packed microtubules may also contribute to the inhibition of RNA trafficking in taiep oligodendrocytes.
本文展示的结果在泰耶普少突胶质细胞中鉴定出一种新的RNA运输表型，该表型增加了反转频率，并限制了含有来自髓鞘碱性蛋白（MBP）mRNA的A2RE运输信号的RNA的运输范围。泰耶普大鼠是一种髓鞘突变体，其特征是少突胶质细胞中微管过度积累以及中枢神经系统髓鞘缺乏。泰耶普RNA运输在发育上与少突胶质细胞中的微管积累相关，并且可以通过用诺考达唑降低微管密度或通过共注射抗动力蛋白抗体抑制动力蛋白活性来部分抑制。这些结果表明，泰耶普少突胶质细胞中的RNA运输受到增强的动力蛋白活性的抑制，这种活性中和或减弱了正端定向运动蛋白驱动蛋白的正常主导力量。少突胶质细胞细突起中微管方向的改变以及密集堆积的微管形成的物理屏障也可能导致泰耶普少突胶质细胞中RNA运输的抑制。
