The intracellular domain of teneurin-2 has a nuclear function and represses zic-1-mediated transcription
The intracellular domain of teneurin-2 has a nuclear function and represses zic-1-mediated transcription
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DOI：
10.1242/jcs.00603
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发表时间：
2003-07-15
影响因子：
4
通讯作者：
Chiquet-Ehrismann, R
中科院分区：
文献类型：
--
作者：
Bagutti, C;Forro, G;Chiquet-Ehrismann, R
Teneurin-2是果蝇配对规则基因ten-m/odz的脊椎动物同源物，被发现是一种膜结合的转录调节因子。在细胞核中，Teneurin-2的胞内结构域与早幼粒细胞白血病(PML)蛋白共存于参与转录调控的核小体中。由于果蝇Ten-M对另一对规则基因OPA的上位性作用，我们研究了哺乳动物OPA同源基因ZIC-1的基因调控是否受到Teneurin-2细胞内结构域的影响。我们发现ZIC介导的载脂蛋白E启动子转录被抑制。Teneurin-2胞内区的释放可被胞外区的亲和性相互作用所刺激，而胞内区被蛋白酶体抑制剂稳定。我们之前已经证明，Teneurin-2由属于同一功能回路的神经元表达。因此，我们假设，亲性相互作用使神经元能够识别它们的靶点，并且一旦进行了适当的接触，Teneurin-2胞内结构域的释放为它们提供了将其基因表达程序从生长切换到分化的信号。
Teneurin-2, a vertebrate homologue of the Drosophila pair-rule gene ten-m/odz, is revealed to be a membrane-bound transcription regulator. In the nucleus, the intracellular domain of teneurin-2 colocalizes with promyelocytic leukemia (PML) protein in nuclear bodies implicated in transcription control. Since Drosophila ten-m acts epistatically to another pair-rule gene opa, we investigated whether gene regulation by the mammalian opa homologue zic-1 was influenced by the intracellular domain of teneurin-2. We found that zic-mediated transcription from the apolipoprotein E promoter was inhibited. Release of the intracellular domain of teneurin-2 could be stimulated by homophilic interaction of the extracellular domain, and the intracellular domain was stabilized by proteasome inhibitors. We have previously shown that teneurin-2 is expressed by neurons belonging to the same functional circuit. Therefore, we hypothesize that homophilic interaction enables neurons to identify their targets and that the release of the intracellular domain of teneurin-2 provides them with a signal to switch their gene expression program from growth towards differentiation once the proper contact has been made.