Institute of Molecular and Cellular Biology, National Taiwan University, Taipei 10617, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
J Biol Chem. 2013 Mar 22;288(12):8391-8404. doi: 10.1074/jbc.M112.408179. Epub 2013 Jan 14.
In this study, the first nestin isoform, Nes-S, was identified in neurons of dorsal root ganglia (DRG) of adult rats. Nes-S cannot form filaments by itself in cytoplasmic intermediate filament-free SW13 cells. Instead, it co-assembles into filaments with vimentin when transfected into vimentin(+) SW13 cells, and with peripherin and neurofilament proteins when transfected into N2a cells. In primary DRG neurons, endogenous Nes-S co-assembles with peripherin and neurofilament proteins. The expression of Nes-S first appears in DRG at postnatal day 5 and persists to adulthood. Among the adult tissues we examined, the expression of Nes-S is restricted to the sensory and motor neurons. Finally, exogenous Nes-S enhances viability when transfected into N2a cells, and knockdown of endogenous Nes-S impairs the survival of DRG neurons in primary cultures. Taken together, Nes-S is a new neuronal intermediate filament protein that exerts a cytoprotective function in mature sensory and motor neurons.
在这项研究中，首次在成年大鼠背根神经节（DRG）神经元中鉴定出巢蛋白的第一个同工型 Nes-S。Nes-S 本身不能在细胞质无中间丝的 SW13 细胞中形成纤维。相反，当转染到波形蛋白阳性的 SW13 细胞中时，它与波形蛋白共同组装成纤维，当转染到 N2a 细胞中时，它与外周蛋白和神经丝蛋白共同组装成纤维。在原代 DRG 神经元中，内源性 Nes-S 与外周蛋白和神经丝蛋白共同组装。Nes-S 的表达最早出现在出生后第 5 天的 DRG 中，并持续到成年期。在我们检查的成年组织中，Nes-S 的表达仅限于感觉神经元和运动神经元。最后，外源性 Nes-S 增强了转染到 N2a 细胞中的活力，而内源性 Nes-S 的敲低则损害了原代培养中 DRG 神经元的存活。总之，Nes-S 是一种新的神经元中间丝蛋白，在成熟的感觉神经元和运动神经元中发挥细胞保护作用。
