Overexpression of Full-length but Not N-terminal Truncated Isoform of Microtubule-associated Protein (MAP) 1B Accelerates Apoptosis of Cultured Cortical Neurons*
Overexpression of Full-length but Not N-terminal Truncated Isoform of Microtubule-associated Protein (MAP) 1B Accelerates Apoptosis of Cultured Cortical Neurons*
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微管相关蛋白 (MAP) 1B 全长而非 N 末端截短亚型的过度表达可加速培养的皮质神经元的凋亡*
DOI：
10.1074/jbc.m210091200
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Y. Uchida
中科院分区：
文献类型：
--
作者：
Y. Uchida
β-淀粉样蛋白（Aβ）被认为在阿尔茨海默病（AD）中起致病作用。然而，在Aβ沉积和神经元损失或痴呆之间存在不完全的相关性。为了阐明神经元对Aβ的反应，通过差异显示和北方印迹分析了Aβ诱导的培养皮层神经元基因表达。在此，我们报道了在Aβ破坏细胞膜之前，非聚集或聚集的Aβ诱导微管相关蛋白1B（MAP 1B）mRNA，特别是含有外显子3U的选择性转录本。含有外显子3U的替代转录物被翻译成N-末端截短的较短的MAP 1B同种型。转染实验表明，这种异构体的过度表达并不加速皮质神经元的轴突生长或凋亡。与此相反，过表达的MAP 1B片段的N-末端126个氨基酸促进神经突起生长和神经元凋亡。这些结果表明，Aβ不会直接诱导有害的全长MAP 1B，但全长MAP 1B的过表达可能作为与细胞骨架异常相关的神经退行性疾病中细胞死亡的效应子。
β-amyloid (Aβ) is presumed to play a pathogenic role in Alzheimer's disease (AD). However, there is an imperfect correlation between Aβ deposition and neuronal loss or dementia. To clarify neuronal responses to Aβ, Aβ-induced gene expression in cultured cortical neurons was analyzed by differential display followed by Northern blotting. Here we report that nonaggregated or aggregated Aβ induced microtubule-associated protein 1B (MAP1B) mRNA, especially the alternative transcript containing exon 3U, before disruption of the cell membrane by Aβ. An alternative transcript containing exon 3U is translated into an N-terminal truncated shorter isoform of MAP1B. Transfection experiments reveal that overexpression of this isoform does not accelerate neurite outgrowth or apoptosis of cortical neurons. In contrast, overexpression of MAP1B fragments containing the N-terminal 126 amino acids promoted neurite outgrowth and neuronal apoptosis. These results suggest that Aβ does not induce deleterious full-length MAP1B directly, but overexpression of full-length MAP1B might act as an effector of cell death in neurodegenerative disorders related to cytoskeletal abnormalities.
大鼠微管相关蛋白 (MAP1B) 编码 cDNA 5 端的分离和测序。
影响因子：
3.5
作者：
Liu,D;Fischer,I
通讯作者：
Fischer,I
PC12 细胞中两种神经生长因子诱导的多肽的鉴定。
DOI：
10.1007/bf02896841
发表时间：
1990
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Sussman,MA;Battenberg,E;Bloom,FE;Fowler,VM
通讯作者：
Fowler,VM