Nesprin-1α contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope
Nesprin-1α contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope
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DOI：
10.1016/j.yexcr.2004.10.009
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发表时间：
2005-02-15
影响因子：
3.7
通讯作者：
Kapiloff, MS
中科院分区：
文献类型：
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作者：
Pare, GC;Easlick, JL;Kapiloff, MS
肌肉 A 激酶锚定蛋白 (mAKAP) 是一种支架蛋白，主要存在于横纹肌细胞的核膜中。 mAKAP 维持由多种信号转导分子组成的复合体，包括 cAMP 依赖性蛋白激酶 A、兰尼碱受体钙释放通道、磷酸二酯酶 4D3 型和蛋白磷酸酶 2A。通过一种未知的机制，包含血影蛋白重复序列的结构域负责将 mAKAP 靶向核膜。我们现在证明，整合膜蛋白 nesprin-1alpha 作为心肌细胞核膜上 mAKAP 的受体。 Nesprin-1alpha 通过保守的 C 端 klarsicht 相关跨膜结构域插入核膜，并通过氨基端血影蛋白重复结构域的结合形成同二聚体。通过 nesprin-1alpha 氨基末端二聚化结构域与第三个 mAKAP 血影蛋白重复序列的直接结合，nesprin-1alpha 将 mAKAP 靶向核膜。反过来，肌细胞中这些血影蛋白重复结构域的过度表达可以取代 nesprin-1alpha 中的 mAKAP。 (C) 2004 Elsevier Inc. 保留所有权利。
Muscle A-kinase anchoring protein (mAKAP) is a scaffold protein found principally at the nuclear envelope of striated myocytes. mAKAP maintains a complex consisting of multiple signal transduction inolecules including the cAMP-dependent protein kinase A, the ryanodine receptor calcium release channel, phosphodiesterase type 4D3, and protein phosphatase 2A. By an unknown mechanism, a domain containing spectrin repeats is responsible for targeting mAKAP to the nuclear envelope. We now demonstrate that the integral membrane protein nesprin-1alpha serves as a receptor for mAKAP on the nuclear envelope in cardiac myocytes. Nesprin-1alpha is inserted into the nuclear envelope by a conserved, C-terminal, klarsicht-related transmembrane domain and forms homodimers by the binding of an amino-terminal spectrin repeat domain. Through the direct binding of the nesprin-1alpha amino-terminal dimerization domain to the third mAKAP spectrin repeat, nesprin-1alpha targets mAKAP to the nuclear envelope. In turn, overexpression of these spectrin repeat domains in myocytes can displace mAKAP from nesprin-1alpha. (C) 2004 Elsevier Inc. All rights reserved.