Bartelt-Kirbach Britta, Moron Margarethe, Glomb Maximilian, Beck Clara-Maria, Weller Marie-Pascale, Golenhofen Nikola
Institute of Anatomy and Cell Biology, University of Ulm, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
Cell Mol Life Sci. 2016 Oct;73(19):3761-75. doi: 10.1007/s00018-016-2219-9. Epub 2016 Apr 16.
The small heat shock protein ΗspΒ5 (αB-crystallin) exhibits generally cytoprotective functions and possesses powerful neuroprotective capacity in the brain. However, little is known about the mode of action of ΗspΒ5 or other members of the HspB family particularly in neurons. To get clues of the neuronal function of HspBs, we overexpressed several HspBs in cultured rat hippocampal neurons and investigated their effect on neuronal morphology and stress resistance. Whereas axon length and synapse density were not affected by any HspB, dendritic complexity was enhanced by HspB5 and, to a lesser extent, by HspB6. Furthermore, we could show that this process was dependent on phosphorylation, since a non-phosphorylatable mutant of HspB5 did not show this effect. Rarefaction of the dendritic arbor is one hallmark of several neurodegenerative diseases. To investigate if HspB5, which is upregulated at pathophysiological conditions, might be able to protect dendrites during such situations, we exposed HspB5 overexpressing neuronal cultures to heat shock. HspB5 prevented heat shock-induced rarefaction of dendrites. In conclusion, we identified regulation of dendritic complexity as a new function of HspB5 in hippocampal neurons.
小热休克蛋白HspB5（αB-晶状体蛋白）通常具有细胞保护功能，在大脑中具有强大的神经保护能力。然而，关于HspB5或HspB家族其他成员的作用模式，尤其是在神经元中的作用模式，人们知之甚少。为了探寻HspB在神经元中的功能线索，我们在培养的大鼠海马神经元中过表达了几种HspB，并研究了它们对神经元形态和抗逆性的影响。虽然轴突长度和突触密度不受任何HspB的影响，但HspB5增强了树突复杂性，HspB6在较小程度上也有此作用。此外，我们可以证明这一过程依赖于磷酸化，因为HspB5的非磷酸化突变体没有显示出这种作用。树突分支减少是几种神经退行性疾病的一个标志。为了研究在病理生理条件下上调的HspB5是否能够在这种情况下保护树突，我们将过表达HspB5的神经元培养物暴露于热休克中。HspB5可防止热休克诱导的树突分支减少。总之，我们确定了树突复杂性的调节是HspB5在海马神经元中的一项新功能。
