Shain W, Forman D S, Madelian V, Turner J N
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
J Cell Biol. 1987 Nov;105(5):2307-14. doi: 10.1083/jcb.105.5.2307.
Astroglial cells in vivo and in vitro respond to hormones, growth factors, and neurotransmitters by changing from an epithelial-like to stellate morphology. We have studied the temporal relationship between receptor activation, second messenger mobilization, and morphological changes using LRM55 astroglial cells. Maintenance of an altered morphology required continuous beta-adrenergic receptor activation. These changes appeared to be mediated by cAMP since they were elicited by its analogue, dibutyryl cAMP, and by forskolin, a direct activator of adenylate cyclase. Changes in cell morphology may require a relatively small increase in intracellular cAMP, since receptor-stimulated changes in cAMP levels were transient and peaked approximately 5 min after receptor activation while changes in morphology took at least 30 min to reach a new steady state. Time-lapse videomicroscopy and high voltage electron microscopy indicated that receptor activation resulted in a sequence of morphological events. Time-lapse observations revealed the development and enlargement of openings through the cytoplasm associated with cytoplasmic withdrawal to the perinuclear region and process formation. Higher resolution high voltage electron microscopy indicated that the transition to a stellate morphology was preceded by the appearance of two distinct cytoplasmic domains. One contained an open network of filaments and organelles. The other was characterized by short broad cytoplasmic filaments. The first domain was similar to cytoplasm in control cells while the second was associated with the development and enlargement of openings through the cytoplasm and regions of obvious cytoplasmic withdrawal.
体内和体外的星形胶质细胞会通过从上皮样形态转变为星状形态来对激素、生长因子和神经递质做出反应。我们使用LRM55星形胶质细胞研究了受体激活、第二信使动员和形态变化之间的时间关系。维持改变后的形态需要持续的β-肾上腺素能受体激活。这些变化似乎是由环磷酸腺苷(cAMP)介导的,因为它们可由其类似物二丁酰环磷酸腺苷以及腺苷酸环化酶的直接激活剂福斯可林引发。细胞形态的变化可能只需要细胞内cAMP相对少量的增加,因为受体刺激引起的cAMP水平变化是短暂的,在受体激活后约5分钟达到峰值,而形态变化至少需要30分钟才能达到新的稳定状态。延时视频显微镜和高电压电子显微镜显示受体激活会导致一系列形态学事件。延时观察揭示了与细胞质向核周区域退缩和突起形成相关的细胞质中开口的形成和扩大。更高分辨率的高电压电子显微镜表明,在转变为星状形态之前会出现两个不同的细胞质区域。一个区域包含开放的细丝和细胞器网络。另一个区域的特征是短而宽的细胞质细丝。第一个区域类似于对照细胞中的细胞质,而第二个区域与细胞质中开口的形成和扩大以及明显的细胞质退缩区域有关。