UCL Institute of Ophthalmology, University College London, London, EC1Y 8TB, UK; Department of Histology, University of Medicine and Pharmacy, Tîrgu Mureş, Romania.
Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, 1117, Hungary.
J Trace Elem Med Biol. 2018 Sep;49:222-230. doi: 10.1016/j.jtemb.2017.12.009. Epub 2017 Dec 27.
Tubulin Polymerization Promoting Protein (TPPP/p25) modulates the dynamics and stability of the microtubule network by its bundling and acetylation enhancing activities that can be modulated by the binding of zinc to TPPP/p25. Its expression is essential for the differentiation of oligodendrocytes, the major constituents of the myelin sheath, and has been associated with neuronal inclusions. In this paper, evidence is provided for the expression and localization of TPPP/p25 in the zinc-rich retina and in the oligodendrocytes in the optic nerve. Localization of TPPP/p25 was established by confocal microscopy using calbindin and synaptophysin as markers of specific striations in the inner plexiform layer (IPL) and presynaptic terminals, respectively. Postsynaptic nerve terminals in striations S1, S3 and S5 in the IPL and a subset of amacrine cells show immunopositivity against TPPP/p25 both in mice and human eyes. The co-localization of TPPP/p25 with acetylated tubulin was detected in amacrine cells, oligodendrocyte cell bodies and in synapses in the IPL. Quantitative Western blot revealed that the TPPP/p25 level in the retina was 0.05-0.13 ng/μg protein, comparable to that in the brain. There was a central (from optic nerve head) to peripheral retinal gradient in TPPP/p25 protein levels. Our in vivo studies revealed that the oral zinc supplementation of mice significantly increased TPPP/p25 as well as acetylated tubulin levels in the IPL. These results suggest that TPPP/p25, a microtubule stabilizer can play a role in the organization and reorganization of synaptic connections and visual integration in the eye.
微管成核促进蛋白（TPPP/p25）通过其束集和乙酰化增强活性来调节微管网络的动力学和稳定性，而这种活性可以通过锌与 TPPP/p25 的结合来调节。它的表达对于少突胶质细胞的分化是必不可少的，少突胶质细胞是髓鞘的主要成分，并与神经元包涵体有关。本文提供了 TPPP/p25 在富含锌的视网膜和视神经中的少突胶质细胞中的表达和定位的证据。通过使用钙结合蛋白和突触小体作为内丛状层 (IPL) 中特定条纹的标志物和突触前末端，分别使用共聚焦显微镜确定了 TPPP/p25 的定位。在 IPL 中的条纹 S1、S3 和 S5 中的突触后神经末梢和一组无长突细胞对 TPPP/p25 表现出免疫阳性，无论是在小鼠还是人眼中。在 IPL 中的无长突细胞、少突胶质细胞体和突触中检测到 TPPP/p25 与乙酰化微管的共定位。定量 Western blot 显示视网膜中的 TPPP/p25 水平为 0.05-0.13ng/μg 蛋白，与大脑中的水平相当。TPPP/p25 蛋白水平在视网膜中从中央（视神经头部）到周边呈梯度分布。我们的体内研究表明，给小鼠口服补锌可显著增加 IPL 中的 TPPP/p25 和乙酰化微管的水平。这些结果表明，微管稳定剂 TPPP/p25 可以在眼睛中的突触连接的组织和重组以及视觉整合中发挥作用。
