The intracellular domain of teneurin-1 interacts with MBD1 and CAP/ponsin resulting in subcellular codistribution and translocation to the nuclear matrix
The intracellular domain of teneurin-1 interacts with MBD1 and CAP/ponsin resulting in subcellular codistribution and translocation to the nuclear matrix
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DOI：
10.1016/j.yexcr.2004.12.020
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发表时间：
2005-04-15
影响因子：
3.7
通讯作者：
Chiquet-Ehrismann, R
中科院分区：
文献类型：
--
作者：
Nunes, SM;Ferralli, J;Chiquet-Ehrismann, R
Teneurin-1 是一种 11 型跨膜蛋白，在发育中和成年中枢神经系统的神经元中表达。为了研究 teneurin-1 的细胞内信号传导，我们寻找与其细胞内结构域相互作用的蛋白质。鉴定出的蛋白质之一是 cCbl 相关蛋白 CAP/ponsin，这是一种包含 SH3 结构域的接头蛋白。这种相互作用一方面导致 teneurin-1 的可溶性细胞内结构域募集到富含 CAP/桥蛋白的细胞膜上。另一方面，它导致 CAP/ponsin 易位至细胞核，细胞核是 teneurin-1 细胞内结构域积累的主要部位。确定的第二个相互作用蛋白是甲基 CpG 结合蛋白 MBD1。在细胞核中，teneurin-1 的胞内结构域与该转录抑制因子共定位于与核基质相关的病灶中。我们认为这些相互作用是特定信号传导途径的一部分。通过检测鸡胚成纤维细胞核斑点中的内源 teneurin-1 免疫活性，获得了细胞内结构域裂解和核易位的证据。此外，在这些细胞的核基质部分以及表达激素诱导型全长 teneurin-1 蛋白的细胞中，可以检测到与单独用胞内结构域转染的细胞中相同大小的 teneurin-1 片段。 (c) 2004 Elsevier Inc. 保留所有权利。
Teneurin-1 is a type 11 transmembrane protein expressed in neurons of the developing and adult central nervous system. To investigate the intracellular signaling of teneurin-1, we searched for proteins interacting with its intracellular domain. One of the proteins identified is the cCbl-associated protein CAP/ponsin, an adaptor protein containing SH3 domains. This interaction results on one hand in the recruitment of the soluble intracellular domain of teneurin-1 to the cell membrane enriched in CAP/ponsin. On the other hand, it leads to the translocation of CAP/ponsin to the nucleus, the major site of accumulation of the intracellular domain of teneurin-1. The second interacting protein identified is the methyl-CpG binding protein MBD1. In the nucleus, the intracellular domain of teneurin-1 colocalizes with this transcriptional repressor in foci associated with the nuclear matrix. We propose that these interactions are part of a specific signaling pathway. Evidence for cleavage and nuclear translocation of the intracellular domain has been obtained by the detection of endogenous teneurin-1 imumoreactivity in nuclear speckles in chick embryo fibroblasts. Furthermore, in the nuclear matrix fraction of these cells as well as in cells expressing a hormone-inducible full-length teneurin-1 protein, a teneurin-1 fragment of identical size could be detected as in cells transfected with the intracellular domain alone. (c) 2004 Elsevier Inc. All rights reserved.