Rudge J S, Li Y, Pasnikowski E M, Mattsson K, Pan L, Yancopoulos G D, Wiegand S J, Lindsay R M, Ip N Y
Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591.
Eur J Neurosci. 1994 May 1;6(5):693-705. doi: 10.1111/j.1460-9568.1994.tb00981.x.
Until recently, astrocytes were not considered as sites for neurotrophic factor action. We show here that, both in vivo and in vitro, astrocytes express receptors for two separate families of neurotrophic factors. In the intact adult rat CNS, astrocytes express the extracellular domain of the neurotrophin receptor TrkB and, in a more restricted population, the low-affinity nerve growth factor receptor p75LNGFR. In the lesioned CNS, expression of the alpha component of the receptor for ciliary neurotrophic factor (CNTFR alpha) switches from a purely neuronal localization to cells in the glial scar at the edge of the wound. Using cultured hippocampal astrocytes as a model to address the functional status of these receptors, we have found only the truncated forms of TrkB and TrkC, which are incapable of signal transduction as measured by protein tyrosine phosphorylation or immediate early gene induction. In contrast, a fully functional CNTF receptor complex capable of signal transduction is present on cultured astrocytes. Thus, the neurotrophin receptors may act primarily to sequester or present the neurotrophins, whereas in the case of CNTF a functional response can be initiated within the astrocyte.
直到最近,星形胶质细胞还未被视为神经营养因子发挥作用的位点。我们在此表明,无论在体内还是体外,星形胶质细胞都表达两类不同神经营养因子家族的受体。在成年大鼠完整的中枢神经系统(CNS)中,星形胶质细胞表达神经营养因子受体TrkB的胞外结构域,并且在数量较少的细胞群体中,表达低亲和力神经生长因子受体p75LNGFR。在受损的中枢神经系统中,睫状神经营养因子(CNTF)受体α亚基(CNTFRα)的表达从纯粹的神经元定位转变为伤口边缘胶质瘢痕中的细胞。以培养的海马星形胶质细胞作为模型来研究这些受体的功能状态,我们仅发现了TrkB和TrkC的截短形式,通过蛋白质酪氨酸磷酸化或立即早期基因诱导检测,它们无法进行信号转导。相比之下,培养的星形胶质细胞上存在能够进行信号转导的完全功能性CNTF受体复合物。因此,神经营养因子受体可能主要起到隔离或呈递神经营养因子的作用,而对于CNTF而言,在星形胶质细胞内可引发功能性反应。