Rutka J T, Murakami M, Dirks P B, Hubbard S L, Becker L E, Fukuyama K, Jung S, Tsugu A, Matsuzawa K
Division of Neurosurgery, The Hospital for Sick Children, The University of Toronto, Ontario, Canada.
J Neurosurg. 1997 Sep;87(3):420-30. doi: 10.3171/jns.1997.87.3.0420.
In the adult human brain, normal astrocytes constitute nearly 40% of the total central nervous system (CNS) cell population and may assume a star-shaped configuration resembling epithelial cells insofar as the astrocytes remain intimately associated, through their cytoplasmic extensions, with the basement membrane of the capillary endothelial cells and the basal lamina of the glial limitans externa. Although their exact function remains unknown, in the past, astrocytes were thought to subserve an important supportive role for neurons, providing a favorable ionic environment, modulating extracellular levels of neurotransmitters, and serving as spacers that organize neurons. In immunohistochemical preparations, normal, reactive, and neoplastic astrocytes may be positively identified and distinguished from other CNS cell types by the expression of the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). Glial fibrillary acidic protein is a 50-kD intracytoplasmic filamentous protein that constitutes a portion of, and is specific for, the cytoskeleton of the astrocyte. This protein has proved to be the most specific marker for cells of astrocytic origin under normal and pathological conditions. Interestingly, with increasing astrocytic malignancy, there is progressive loss of GFAP production. As the human gene for GFAP has now been cloned and sequenced, this review begins with a summary of the molecular biology of GFAP including the proven utility of the GFAP promoter in targeting genes of interest to the CNS in transgenic animals. Based on the data provided the authors argue cogently for an expanded role of GFAP in complex cellular events such as cytoskeletal reorganization, maintenance of myelination, cell adhesion, and signaling pathways. As such, GFAP may not represent a mere mechanical integrator of cellular space, as has been previously thought. Rather, GFAP may provide docking sites for important kinases that recognize key cellular substrates that enable GFAP to form a dynamic continuum with microfilaments, integrin receptors, and the extracellular matrix.
在成人大脑中，正常星形胶质细胞占中枢神经系统（CNS）细胞总数的近40%，其形态可能呈星形，类似上皮细胞，因为星形胶质细胞通过其细胞质延伸与毛细血管内皮细胞的基底膜和神经胶质界膜的基膜紧密相连。尽管其确切功能尚不清楚，但过去人们认为星形胶质细胞对神经元起着重要的支持作用，提供有利的离子环境，调节神经递质的细胞外水平，并作为组织神经元的间隔物。在免疫组织化学制剂中，正常、反应性和肿瘤性星形胶质细胞可通过星形胶质细胞特异性中间丝胶质纤维酸性蛋白（GFAP）的表达得到阳性鉴定，并与其他中枢神经系统细胞类型区分开来。胶质纤维酸性蛋白是一种50kD的胞质丝状蛋白，是星形胶质细胞细胞骨架的一部分且具有特异性。在正常和病理条件下，该蛋白已被证明是星形胶质细胞起源细胞最特异的标志物。有趣的是，随着星形胶质细胞恶性程度的增加，GFAP的产生逐渐减少。由于GFAP的人类基因现已被克隆和测序，本综述首先总结了GFAP的分子生物学，包括GFAP启动子在转基因动物中将感兴趣的基因靶向中枢神经系统方面已被证实的效用。基于所提供的数据，作者有力地论证了GFAP在细胞骨架重组、髓鞘维持、细胞黏附及信号通路等复杂细胞事件中发挥更广泛的作用。因此，GFAP可能并不像以前认为的那样仅仅是细胞空间的机械整合者。相反，GFAP可能为重要的激酶提供停靠位点，这些激酶识别关键的细胞底物，使GFAP能够与微丝蛋白、整合素受体和细胞外基质形成动态连续体。
