Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal differentiation and neurite outgrowth.
Subcellular rearrangement of hsp90-binding immunophilins accompanies neuronal differentiation and neurite outgrowth.
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DOI：
10.1111/j.1471-4159.2010.06970.x
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发表时间：
2010-11
影响因子：
4.7
通讯作者：
Galigniana MD
中科院分区：
文献类型：
--
作者：
Quintá HR;Maschi D;Gomez-Sanchez C;Piwien-Pilipuk G;Galigniana MD
FKBP 51和FKBP 52是TPR-结构域亲免蛋白，属于结合类固醇受体的TPR-蛋白hsp90 hsp70 p23异源复合物。亲免疫素与受体折叠、亚细胞定位和依赖于酶的转录有关。此外，它们结合免疫抑制剂大环内酯FK506，其通过仍然未知的机制显示神经再生和神经保护作用。在这项研究中，我们证明，在未分化的神经母细胞瘤细胞和胚胎海马神经元，FKBP 52·hsp90·p23杂合物集中在核周结构。在用FK506刺激细胞时，该结构解体，并且该核周区域变得转录活跃。神经元表型的获得伴随着β III-微管蛋白、Map2、Tau-1以及hsp90、hsp70、p23和FKBP 52的表达增加。在早期分化阶段，核周杂合物沿着细胞质和新生神经突重新分布，p23结合到中间丝和微管获得更高的细胞质组织。当FKBP 52向神经突移动并集中在树枝状体和末端轴突中时，表达保持恒定的FKBP 51在核周结构中取代FKBP 52。重要的是，FKBP52过表达或FKBP51敲低有利于神经突生长，而FKBP52敲低或FKBP51过表达则会损害神经突生长，这表明这些FK506结合蛋白之间的平衡在神经元分化的早期机制中起着关键作用。
FKBP51 and FKBP52 are TPR-domain immunophilins belonging to the TPR-protein hsp90 hsp70 p23 heterocomplex bound to steroid receptors. Immunophilins are related to receptor folding, subcellular localization, and hormone-dependent transcription. Also, they bind the immunosuppressant macrolide FK506, which shows neuroregenerative and neuroprotective actions by a still unknown mechanism. In this study, we demonstrate that in both, undifferentiated neuroblastoma cells and embryonic hippocampal neurons, the FKBP52•hsp90•p23 heterocomplex concentrates in a perinuclear structure. Upon cell stimulation with FK506, this structure disassembles and this perinuclear area becomes transcriptionally active. The acquisition of a neuronal phenotype is accompanied by increased expression of βIII-tubulin, Map2, Tau-1, but also hsp90, hsp70, p23, and FKBP52. During the early differentiation steps, the perinuclear heterocomplex redistributes along the cytoplasm and nascent neurites, p23 binds to intermediate filaments and microtubules acquired higher filamentary organization. While FKBP52 moves towards neurites and concentrates in arborization bodies and terminal axons, FKBP51, whose expression remains constant, replaces FKBP52 in the perinuclear structure. Importantly, neurite outgrowth is favored by FKBP52 overexpression or FKBP51 knockdown, and is impaired by FKBP52 knock-down or FKBP51 overexpression, indicating that the balance between these FK506-binding proteins plays a key role during the early mechanism of neuronal differentiation.
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影响因子：
--
作者：
Gold, BG;Zhong, YP
通讯作者：
Zhong, YP
影响因子：
2.9
作者：
Galigniana, MD;Harrell, JM;Pratt, WB
通讯作者：
Pratt, WB
影响因子：
14
作者：
Buttiglione, M.;Vitiello, F.;Gristina, R.
通讯作者：
Gristina, R.
DOI：
10.4161/nucl.1.4.11743
发表时间：
2010-07
期刊：
Nucleus (Austin, Tex.)
影响因子：
--
作者：
Galigniana MD;Echeverría PC;Erlejman AG;Piwien-Pilipuk G
通讯作者：
Piwien-Pilipuk G
影响因子：
2.9
作者：
Consales, Claudia;Volpicelli, Floriana;di Porzio, Umberto
通讯作者：
di Porzio, Umberto