Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU.
Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU.
复制标题
DOI：
10.3389/fnins.2021.643115
复制
发表时间：
2021
影响因子：
4.3
通讯作者：
Zempel H
中科院分区：
文献类型：
--
作者：
Bachmann S;Bell M;Klimek J;Zempel H
在成人大脑中，微管相关蛋白TAU的六种异构体被表达，它们是MAPT基因外显子2、3和10的选择性剪接的结果。这些异构体在N-末端插入(0N、1N、2N)和C-末端重复结构域(3R或4R)的数量上不同，并且根据大脑区域和发育阶段的不同而表达不同。虽然所有的TAU亚型都可以聚集并形成神经原纤维缠结，但一些TAU亚型的特征是聚集在特定的TAU亚型上，如Pick病和进行性核上性麻痹。然而，单个TAU亚型在细胞环境中的影响还没有得到充分的研究。在本报告中，我们研究了人类特异性TAU亚型在原代小鼠神经元中的亚细胞定位，并分析了TAU亚型对人SH-SY5Y神经母细胞瘤细胞面积和微管动力学的影响。我们的结果表明，2N-TAU异构体在轴突分选中被特别保留，轴突丰富与重复结构域的数量无关，但4R-TAU异构体的额外重复结构域导致表达这些特定异构体的细胞普遍缩小，微管数量增加。我们的研究指出，不同的TAU亚型可能通过不同的分类模式和直接对微管动力学的影响而不同地影响微管动力学。
In the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3, and 10 of the MAPT gene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are differentially expressed depending on the brain region and developmental stage. Although all TAU isoforms can aggregate and form neurofibrillary tangles, some tauopathies, such as Pick’s disease and progressive supranuclear palsy, are characterized by the accumulation of specific TAU isoforms. The influence of the individual TAU isoforms in a cellular context, however, is understudied. In this report, we investigated the subcellular localization of the human-specific TAU isoforms in primary mouse neurons and analyzed TAU isoform-specific effects on cell area and microtubule dynamics in human SH-SY5Y neuroblastoma cells. Our results show that 2N-TAU isoforms are particularly retained from axonal sorting and that axonal enrichment is independent of the number of repeat domains, but that the additional repeat domain of 4R-TAU isoforms results in a general reduction of cell size and an increase of microtubule counts in cells expressing these specific isoforms. Our study points out that individual TAU isoforms may influence microtubule dynamics differentially both by different sorting patterns and by direct effects on microtubule dynamics.
登录
查看更多内容
DOI：
10.1083/jcb.201007161
发表时间：
2011-02-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gauthier-Kemper A;Weissmann C;Golovyashkina N;Sebö-Lemke Z;Drewes G;Gerke V;Heinisch JJ;Brandt R
通讯作者：
Brandt R
DOI：
10.1083/jcb.101.4.1371
发表时间：
1985-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Binder LI;Frankfurter A;Rebhun LI
通讯作者：
Rebhun LI
影响因子：
16.2
作者：
GOEDERT, M;SPILLANTINI, MG;CROWTHER, RA
通讯作者：
CROWTHER, RA
影响因子：
11.4
作者：
GOEDERT, M;JAKES, R
通讯作者：
JAKES, R
影响因子：
4.8
作者：
Goode, BL;Chau, M;Feinstein, SC
通讯作者：
Feinstein, SC