Sakry Dominik, Yigit Hatice, Dimou Leda, Trotter Jacqueline
Molecular Cell Biology, Department of Biology, Johannes Gutenberg University Mainz, D-55122 Mainz, Germany.
Physiological Genomics, Biomedical Center, Ludwig-Maximilians University Munich, D-80336 Munich, Germany.
PLoS One. 2015 May 12;10(5):e0127222. doi: 10.1371/journal.pone.0127222. eCollection 2015.
NG2 protein-expressing oligodendrocyte progenitor cells (OPC) are a persisting and major glial cell population in the adult mammalian brain. Direct synaptic innervation of OPC by neurons throughout the brain together with their ability to sense neuronal network activity raises the question of additional physiological roles of OPC, supplementary to generating myelinating oligodendrocytes. In this study we investigated whether OPC express neuromodulatory factors, typically synthesized by other CNS cell types. Our results show that OPC express two well-characterized neuromodulatory proteins: Prostaglandin D2 synthase (PTGDS) and neuronal Pentraxin 2 (Nptx2/Narp). Expression levels of the enzyme PTGDS are influenced in cultured OPC by the NG2 intracellular region which can be released by cleavage and localizes to glial nuclei upon transfection. Furthermore PTGDS mRNA levels are reduced in OPC from NG2-KO mouse brain compared to WT cells after isolation by cell sorting and direct analysis. These results show that OPC can contribute to the expression of these proteins within the CNS and suggest PTGDS expression as a downstream target of NG2 signaling.
表达NG2蛋白的少突胶质前体细胞(OPC)是成年哺乳动物大脑中持续存在的主要胶质细胞群。大脑中神经元对OPC的直接突触支配以及它们感知神经元网络活动的能力,引发了关于OPC除了生成髓鞘少突胶质细胞之外的其他生理作用的问题。在本研究中,我们调查了OPC是否表达通常由其他中枢神经系统细胞类型合成的神经调节因子。我们的结果表明,OPC表达两种特征明确的神经调节蛋白:前列腺素D2合酶(PTGDS)和神经元五聚体蛋白2(Nptx2/Narp)。酶PTGDS的表达水平在培养的OPC中受到NG2细胞内区域的影响,该区域可通过切割释放,并在转染后定位于胶质细胞核。此外,通过细胞分选和直接分析分离后,与野生型细胞相比,NG2基因敲除小鼠大脑中的OPC中PTGDS mRNA水平降低。这些结果表明,OPC可促进中枢神经系统内这些蛋白的表达,并提示PTGDS表达作为NG2信号的下游靶点。