Souza C C R, Dombroski T C D, Machado H R, Oliveira R S, Rocha L B, Rodrigues A R A, Neder L, Chimelli L, Corrêa V M A, Larson R E, Martins A R
Departamento de Neurologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
Braz J Med Biol Res. 2013 Feb;46(2):164-70. doi: 10.1590/1414-431x20122627.
Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98 th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.
肌球蛋白Va作为一种基于肌动蛋白的持续性运动分子,在神经系统中高度富集,负责运输和/或拴系细胞器、囊泡以及mRNA和蛋白质翻译机器。肌球蛋白Va的突变会导致格里斯切利病,该病与严重的神经功能缺陷和较短的寿命相关。尽管肌球蛋白Va在发育过程中发挥着关键作用,但尚未有关于其在人类整个生命周期中枢神经系统中表达情况的报道。为了解决这个问题,我们使用亲和纯化的抗肌球蛋白Va抗体,通过免疫组织化学方法研究了从新生儿到老年人小脑肌球蛋白Va的表达情况。肌球蛋白Va在出生后第10天到98岁的所有年龄段均有表达,分布于小脑的分子层、浦肯野细胞层和颗粒层。除了出生后发育阶段,从儿童期到老年期,小脑肌球蛋白Va的表达在定位或强度上基本没有差异。浦肯野细胞中类似颗粒和攀缘纤维的结构被深度染色。在齿状神经元中,长突起和点状核结构均被抗肌球蛋白Va深度染色。在出生后的第一年,肌球蛋白Va在外侧颗粒层(EGL)中存在差异表达。在EGL中,增殖的前体颗粒细胞未被抗肌球蛋白Va抗体染色。相比之下,EGL中迁移前的颗粒细胞被中度染色。在分子层呈现迁移状态的颗粒细胞也被中度染色。总之,神经元肌球蛋白Va受发育调控,似乎从出生后早期到衰老阶段对小脑功能都是必需的。