Complement component 1q subcomponent binding protein in the brain of the rat

János Barna,Gina Puska,Dávid Kovács,Diána Dimén,Gabriella Pál,Vivien Csikós,Edina B Udvari,Szilvia Oláh,Árpád Dobolyi

doi:10.1038/s41598-019-40788-z

János Barna, Gina Puska + Show 7 more

Open Access

https://doi.org/10.1038/s41598-019-40788-z

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Abstract

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.

Highlights

Complement component 1q subcomponent binding protein (C1qbp; UniGene code: Rn.2765) is a multifunctional and multicompartmental protein[1,2]
C1qbp mRNA was relatively widespread in the brain but it was not found in the white matter
The brain distribution of C1qbp will first be discussed including the specificity of labelling at the mRNA and protein level

Summary

Introduction

Complement component 1q subcomponent binding protein (C1qbp; UniGene code: Rn.2765) is a multifunctional and multicompartmental protein[1,2]. While the importance of this change has not been elucidated, it has been reported that cytosolic C1qbp can interact with the intracellular loop of different G-protein coupled receptors including beta subunits of GABAA receptors[49], vasopressin[50] and adrenergic receptors[51,52] and alter their ligand binding properties[50] or subcellular localization[51]. Acting via these receptors or by altering energy availability for brain cell compartments, are potential mechanisms how C1qbp can affect information transmission in the central nervous system. Pre- and post-embedding immunoelectron microscopy and double fluorescent labelling with the mitochondrial marker isocitrate dehydrogenase subunit alpha (Idh3a) was applied to determine the subcellular localization of C1qbp in some neurons containing a substantial amount of the protein

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Conclusion