肌萎缩侧索硬化症相关肉瘤融合蛋白与应激颗粒-中国细胞生物学学报.PDF

871中国细胞生物学学报 Chinese Journal of Cell Biology 2016, 38(7): 850–856 DOI: 10.11844/cj cb.2016.07.0067 综述 肌萎缩侧索硬化症相关肉瘤融合蛋白与应激颗粒 * 魏砚明 栾智华 陈秀红 梁 锐 ( 山西中医学院实验中心, 晋中030619) 摘要 肌萎缩侧索硬化症(amyotrophic lateral sclerosis, ALS)是一种以运动神经细胞死亡为 特征的、致命性神经退行性疾病。作为一种RNA结合蛋白, 肉瘤融合蛋白(fused in sarcoma, FUS) 突变引起ALS。应激颗粒(stress granules, SG)是细胞在应激条件下产生的细胞质结构。FUS存在于 SG 中, SG标记物是FUS阳性聚集体的组分, 提示FUS突变体可能干扰SG正常功能, 并且SG可能作 为病理性FUS聚集体的前体。该文探讨了SG募集FUS的机制与调控, 分析了SG与FUS聚集体之间 的关系, 以期为了解SG在FUS突变引起的ALS发生中的作用提供参考。 关键词 肌萎缩侧索硬化症; 肉瘤融合蛋白; 应激颗粒 Amyotrophic Lateral Sclerosis Associated FUS Protein and Stress Granule Wei Yanming*, Luan Zhihua, Chen Xiuhong, Liang Rui (Experimental Centre, Shanxi University of Traditional Chinese Medicine, Jinzhong 030619, China) Abstract Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by loss of motor neurons. As a RNA binding protein, fused in sarcoma (FUS) mutations cause ALS. Stress granules (SG) are cytosolic structures formed normally in response to induced stressors. FUS assembles into SG, while SG marker proteins are constituents of pathological FUS aggregates, implying that mutant FUS could disturb the function of SG and FUS aggregates might arise from SG. This review will discuss the mechanisms and regulation that FUS recruit into SG, analyze the relationship between SG and FUS aggregates, and provide implications for the roles of SG in FUS mutants caused ALS. Keywords amyotrophic lateral sclerosis; fused in sarcoma; stress granule 肌萎缩侧索硬化症(amyotrophic lateral sclerosis, 蛋白, 参与多种RNA代谢过程[1-2] 。目前对于FUS突 ALS)是一种致命性运动神经细胞疾病。绝大多数 变引起ALS的机制仍未阐明。 ALS病例为发病原因不明的散发性ALS, 其余