Kelić S, Levy S, Suarez C, Weinstein D E
Department of Neuroscience, Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York, 10461, USA.
Mol Cell Neurosci. 2001 Mar;17(3):551-60. doi: 10.1006/mcne.2000.0955.
Astrocytes respond to contact with neurons by cell-cycle arrest and complex process formation. In our effort to discover the molecular mechanisms that underlie this phenomenon we have identified a known tetraspanin, CD81, as a critical component of astrocyte responses to neuronal differentiation signals. Here we show that CD81 is expressed on the surface of the astrocyte and that its expression level can be modulated by contact with neurons. Further, using three separate antibodies, 2F7, Eat1, and Eat2, which recognize unique epitopes in the extracellular domains of the CD81 protein, we show that there is a unique domain, recognized by Eat1, that is required for astrocyte cell-cycle withdrawal in response to neurons. This is likely due to conformational changes in the CD81 molecule, as inclusion of 2F7 actually augments neuron-induced astrocyte growth arrest. The critical nature of CD81 in normal astrocyte-neuron biology was confirmed by using mice in which CD81 had been deleted by homologous recombination. Astrocytes null at the CD81 locus were blind to the proliferative arrest encoded on the neuronal cell surface. Taken together, these data strongly suggest that CD81 is a critical regulator of neuron-induced astrocytic differentiation.
星形胶质细胞通过细胞周期停滞和复杂过程形成对与神经元的接触做出反应。在我们探索这一现象背后分子机制的过程中，我们确定了一种已知的四跨膜蛋白CD81，它是星形胶质细胞对神经元分化信号反应的关键组成部分。在此我们表明，CD81在星形胶质细胞表面表达，并且其表达水平可通过与神经元接触来调节。此外，使用三种分别识别CD81蛋白胞外结构域中独特表位的抗体2F7、Eat1和Eat2，我们发现存在一个由Eat1识别的独特结构域，它是星形胶质细胞响应神经元而退出细胞周期所必需的。这可能是由于CD81分子的构象变化，因为加入2F7实际上增强了神经元诱导的星形胶质细胞生长停滞。通过使用通过同源重组删除了CD81的小鼠，证实了CD81在正常星形胶质细胞 - 神经元生物学中的关键性质。在CD81基因座缺失的星形胶质细胞对神经元细胞表面编码的增殖停滞无反应。综上所述，这些数据强烈表明CD81是神经元诱导的星形胶质细胞分化的关键调节因子。
