Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
MTA-ELTE Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary.
Sci Rep. 2019 Mar 14;9(1):4597. doi: 10.1038/s41598-019-40788-z.
Complement component 1q subcomponent binding protein (C1qbp) is a multifunctional protein involved in immune response, energy homeostasis of cells as a plasma membrane receptor, and a nuclear, cytoplasmic or mitochondrial protein. Recent reports suggested its neuronal function, too, possibly in axon maintenance, synaptic function, and neuroplasticity. Therefore, we addressed to identify C1qbp in the rat brain using in situ hybridization histochemistry and immunolabelling at light and electron microscopic level. C1qbp has a topographical distribution in the brain established by the same pattern of C1qbp mRNA-expressing and protein-containing neurons with the highest abundance in the cerebral cortex, anterodorsal thalamic nucleus, hypothalamic paraventricular (PVN) and arcuate nuclei, spinal trigeminal nucleus. Double labelling of C1qbp with the neuronal marker NeuN, with the astrocyte marker S100, and the microglia marker Iba1 demonstrated the presence of C1qbp in neurons but not in glial cells in the normal brain, while C1qbp appeared in microglia following their activation induced by focal ischemic lesion. Only restricted neurons expressed C1qbp, for example, in the PVN, magnocellular neurons selectively contained C1qbp. Further double labelling by using the mitochondria marker Idh3a antibody suggested the mitochondrial localization of C1qbp in the brain, confirmed by correlated light and electron microscopy at 3 different brain regions. Post-embedding immunoelectron microscopy also suggested uneven C1qbp content of mitochondria in different brain areas but also heterogeneity within single neurons. These data suggest a specific function of C1qbp in the brain related to mitochondria, such as the regulation of local energy supply in neuronal cells.
补体成分 1q 亚基结合蛋白（C1qbp）是一种多功能蛋白，参与免疫反应、细胞能量稳态作为质膜受体，以及核、细胞质或线粒体蛋白。最近的报告表明它也具有神经元功能，可能在轴突维持、突触功能和神经可塑性中发挥作用。因此，我们使用原位杂交组织化学和免疫标记在光镜和电镜水平上确定大鼠脑中的 C1qbp。C1qbp 在脑中具有由 C1qbp mRNA 表达和含蛋白神经元相同模式建立的拓扑分布，在大脑皮层、前背丘脑核、下丘脑室旁核和弓状核中含量最高，三叉神经脊核。C1qbp 与神经元标志物 NeuN、星形胶质细胞标志物 S100 和小胶质细胞标志物 Iba1 的双重标记表明 C1qbp 存在于神经元中，但不存在于正常脑中的神经胶质细胞中，而 C1qbp 在小胶质细胞激活后出现。只有有限的神经元表达 C1qbp，例如在室旁核中，大神经元选择性地含有 C1qbp。使用线粒体标志物 Idh3a 抗体进行进一步的双重标记表明 C1qbp 在大脑中的线粒体定位，在 3 个不同脑区的相关光镜和电镜下得到证实。后包埋免疫电镜还表明不同脑区线粒体的 C1qbp 含量不均匀，但单个神经元内也存在异质性。这些数据表明 C1qbp 在大脑中具有与线粒体相关的特定功能，例如调节神经元细胞中的局部能量供应。
