The hsp90-FKBP52 Complex Links the Mineralocorticoid Receptor to Motor Proteins and Persists Bound to the Receptor in Early Nuclear Events
The hsp90-FKBP52 Complex Links the Mineralocorticoid Receptor to Motor Proteins and Persists Bound to the Receptor in Early Nuclear Events
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DOI：
10.1128/mcb.01190-09
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发表时间：
2010-03-01
影响因子：
5.3
通讯作者：
Piwien-Pilipuk, Graciela
中科院分区：
文献类型：
--
作者：
Galigniana, Mario D.;Erlejman, Alejandra G.;Piwien-Pilipuk, Graciela
在这项研究中，我们表明，盐皮质激素受体（MR）的亚细胞定位的调节tetratricopeptide域（TPR）蛋白。高分子量亲免素（IMM）FKBP 52将MR-hsp 90复合物与动力蛋白/动力肌动蛋白马达连接，有利于MR的细胞质转运到细胞核。FKBP 51或TPR肽取代这种HSP 90结合IMM有利于MR的细胞质定位。完整的运动机制，包括动力蛋白和微管蛋白，可以从紫杉醇/GTP稳定的胞质溶胶中回收，并在剥离的MR免疫颗粒上完全重新组装。整个MR-hsp 90为基础的杂复合物与醛固酮孵育10分钟后，在细胞核的可溶性部分中瞬时恢复。此外，交联的MR-hsp 90杂合物在细胞核中积累的依赖性的方式，表明杂合物可以通过未解离通过核孔。另一方面，一个肽，包括MR的DNA结合结构域损害MR的核输出，这表明该结构域的参与过程。这项研究代表了第一份报告，描述了整个分子系统，命令MR核质运输，并提出了MR-hsp 90-TPR蛋白杂合物是在细胞核中，而不是在细胞质中解离。
In this study, we demonstrate that the subcellular localization of the mineralocorticoid receptor (MR) is regulated by tetratricopeptide domain (TPR) proteins. The high-molecular-weight immunophilin (IMM) FKBP52 links the MR-hsp90 complex to dynein/dynactin motors favoring the cytoplasmic transport of MR to the nucleus. Replacement of this hsp90-binding IMM by FKBP51 or the TPR peptide favored the cytoplasmic localization of MR. The complete movement machinery, including dynein and tubulin, could be recovered from paclitaxel/GTP-stabilized cytosol and was fully reassembled on stripped MR immune pellets. The whole MR-hsp90-based heterocomplex was transiently recovered in the soluble fraction of the nucleus after 10 min of incubation with aldosterone. Moreover, cross-linked MR-hsp90 heterocomplexes accumulated in the nucleus in a hormone-dependent manner, demonstrating that the heterocomplex can pass undissociated through the nuclear pore. On the other hand, a peptide that comprises the DNA-binding domain of MR impaired the nuclear export of MR, suggesting the involvement of this domain in the process. This study represents the first report describing the entire molecular system that commands MR nucleocytoplasmic trafficking and proposes that the MR-hsp90-TPR protein heterocomplex is dissociated in the nucleus rather than in the cytoplasm.