HspB5/αB-crystallin phosphorylation at S45 and S59 is essential for protection of the dendritic tree of rat hippocampal neurons,Journal of Neurochemistry

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HspB5/αB-crystallin phosphorylation at S45 and S59 is essential for protection of the dendritic tree of rat hippocampal neurons
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2020-11-21 , DOI: 10.1111/jnc.15247
Britta Bartelt-Kirbach ₁ , Christoph Wiegreffe ₂ , Samuel Birk ₁ , Tina Baur ₁ , Margarethe Moron ₁ , Stefan Britsch ₂ , Nikola Golenhofen ₁

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Rarefaction of the dendritic tree leading to neuronal dysfunction is a hallmark of many neurodegenerative diseases and we have shown previously that heat shock protein B5 (HspB5)/αB-crystallin is able to increase dendritic complexity in vitro. The aim of this study was to investigate if this effect is also present in vivo, if HspB5 can counteract dendritic rarefaction under pathophysiological conditions and the impact of phosphorylation of HspB5 in this process. HspB5 and eight mutants inhibiting or mimicking phosphorylation at the three phosphorylation sites serine (S)19, S45, and S59 were over-expressed in cultured rat hippocampal neurons with subsequent investigation of the complexity of the dendritic tree. Sholl analysis revealed significant higher complexity of the dendritic tree after over-expression of wild-type HspB5 and the mutant HspB5-AEE. All other mutants showed no or minor effects. For in vivo investigation in utero electroporation of mouse embryos was applied. At embryonal day E15.5 the respective plasmids were injected, cornu ammonis 1 (CA1) pyramidal cells transfected by electroporation and their basal dendritic trees were analyzed at post-natal day P15. In vivo, HspB5 and HspB5-AEE led to an increase of total dendritic length as well as a higher complexity. Finally, the dendritic effect of HspB5 was investigated under a pathophysiological condition, that is, iron deficiency which reportedly results in dendritic rarefaction. HspB5 and HspB5-AEE but not the non-phosphorylatable mutant HspB5-AAA significantly counteracted the dendritic rarefaction. Thus, our data suggest that up-regulation and selective phosphorylation of HspB5 in neurodegenerative diseases may preserve dendritic morphology and counteract neuronal dysfunction.

中文翻译：

S45 和 S59 处的 HspB5/αB-晶状体蛋白磷酸化对于保护大鼠海马神经元的树突树至关重要

导致神经元功能障碍的树突树的稀少是许多神经退行性疾病的标志，我们之前已经表明热休克蛋白 B5 (HspB5)/αB-晶状体蛋白能够在体外增加树突复杂性。本研究的目的是调查体内是否也存在这种效应，HspB5 是否可以抵消病理生理条件下的树突稀疏以及 HspB5 磷酸化在该过程中的影响。HspB5 和八个突变体抑制或模仿三个磷酸化位点丝氨酸 (S)19、S45 和 S59 的磷酸化在培养的大鼠海马神经元中过度表达，随后对树突树的复杂性进行了调查。Sholl 分析显示，在过度表达野生型 HspB5 和突变型 HspB5-AEE 后，树突树的复杂性显着提高。所有其他突变体都没有显示出影响或影响很小。应用小鼠胚胎的子宫内电穿孔进行体内研究。在胚胎第 E15.5 天注射相应的质粒，在出生后第 P15 天分析通过电穿孔转染的玉米角 1 (CA1) 锥体细胞及其基底树突树。在体内，HspB5 和 HspB5-AEE 导致总树突长度增加以及更高的复杂性。最后，在病理生理条件下研究了 HspB5 的树突效应，即据报道导致树突稀疏的缺铁。HspB5 和 HspB5-AEE 但不是非磷酸化突变体 HspB5-AAA 显着抵消了树突稀疏。因此，我们的数据表明，神经退行性疾病中 HspB5 的上调和选择性磷酸化可能会保留树突形态并抵消神经元功能障碍。

更新日期：2020-11-21

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