DISTRIBUTION OF THE PHOSPHORYLATED MICROTUBULE-ASSOCIATED PROTEIN-TAU IN DEVELOPING CORTICAL-NEURONS
DISTRIBUTION OF THE PHOSPHORYLATED MICROTUBULE-ASSOCIATED PROTEIN-TAU IN DEVELOPING CORTICAL-NEURONS
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DOI：
10.1016/0306-4522(94)90533-9
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发表时间：
1994-12-01
期刊：
影响因子：
3.3
通讯作者：
COUCK, AM
中科院分区：
文献类型：
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作者：
BRION, JP;OCTAVE, JN;COUCK, AM
在大脑发育过程中，微管相关蛋白tau呈现短暂的高磷酸化状态。我们研究了磷酸化的胎儿型tau在发育中的大鼠皮质和胚胎皮质神经元培养中的发育分布，使用的抗体与tau以磷酸化依赖的方式反应。胎儿型tau蛋白在胚胎发育20d出现于皮质，18d未检测到，在神经细胞培养4~5d才能检测到。细胞周期蛋白依赖性激酶p34(Cdc2)仅在胚胎脑组织的生发层表达，与磷酸化的tau蛋白不共定位。出生后10天，磷酸化的tau逐渐从皮质神经元中消失，首先从最深的皮质层消失，那里的神经元是个体发育最古老的。在各发育阶段的皮质神经元轴突和树突中均发现有磷酸化的tau，而未磷酸化的tau在发育过程中有从树突消失的趋势。与其他发育标记物的表达相比，皮质中磷酸化tau蛋白的出现时间表明，磷酸化tau蛋白仅在神经突起生长旺盛时期处于高水平，在轴突稳定和突触发生期间消失，同时伴随着成年tau亚型的表达。在对照培养和秋水仙素处理的培养中，磷酸化的tau与冷稳定和抗秋水仙碱的微管无关。这些体内结果表明，磷酸化tau的高表达与发育中大脑高可塑性时期动态微管网络的存在有关。
During brain development, the microtubule-associated protein tau presents a transient state of high phosphorylation. We have investigated the developmental distribution of the phosphorylated fetal-type tau in the developing rat cortex and in cultures of embryonic cortical neurons, using antibodies which react with tau in a phosphorylation-dependent manner. The phosphorylated fetal-type tau was present in the developing cortex at 20 days but not at 18 days of embryonic life and was not detected before four to five days in neuronal culture. The cyclin-dependent kinase p34(cdc2) was expressed only in germinal layers in the embryonic brain and was not co-localized with phosphorylated tau. After 10 days of postnatal life, the phosphorylated tau progressively disappeared from cortical neurons, disappearing first from the deepest cortical layers where neurons are ontogenetically the oldest. Phosphorylated tau was found in axons and dendrites of cortical neurons at all developmental stages whereas unphosphorylated tau tended to disappear from dendrites during development. The timing of appearance of phosphorylated tau in the cortex, by comparison with the expression of other developmental markers, indicates that phosphorylated tau is present at a high level only during the period of intense neuritic outgrowth and that it disappears during the period of neurite stabilization and synaptogenesis, concomitantly to the expression of adult tau isoforms. In control cultures and in cultures treated with colchicine, the phosphorylated tau was not associated to cold-stable and to colchicine-resistant microtubules.These in vivo results suggest that the high expression of phosphorylated tau species is correlated with the presence of a dynamic microtubule network during a period of high plasticity in the developing brain.