Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, Magdeburg, Germany.
PLoS One. 2012;7(6):e39710. doi: 10.1371/journal.pone.0039710. Epub 2012 Jun 22.
C-terminal binding proteins (CtBPs) are well-characterized nuclear transcriptional co-regulators. In addition, cytoplasmic functions were discovered for these ubiquitously expressed proteins. These include the involvement of the isoform CtBP1-S/BARS50 in cellular membrane-trafficking processes and a role of the isoform RIBEYE as molecular scaffolds in ribbons, the presynaptic specializations of sensory synapses. CtBPs were suggested to regulate neuronal differentiation and they were implied in the control of gene expression during epileptogenesis. However, the expression patterns of CtBP family members in specific brain areas and their subcellular localizations in neurons in situ are largely unknown. Here, we performed comprehensive assessment of the expression of CtBP1 and CtBP2 in mouse brain at the microscopic and the ultra-structural levels using specific antibodies. We quantified and compared expression levels of both CtBPs in biochemically isolated brain fractions containing cellular nuclei or synaptic compartment. Our study demonstrates differential regional and subcellular expression patterns for the two CtBP family members in brain and reveals a previously unknown synaptic localization for CtBP2 in particular brain regions. Finally, we propose a mechanism of differential synapto-nuclear targeting of its splice variants CtBP2-S and CtBP2-L in neurons.
C 端结合蛋白（CtBPs）是经过充分研究的核转录共调节因子。此外，这些在所有细胞中表达的蛋白还具有细胞质功能。这些功能包括异构体 CtBP1-S/BARS50 参与细胞内的膜运输过程，以及异构体 RIBEYE 作为分子支架在感觉突触的突触前特化结构中的作用。CtBPs 被认为可以调节神经元分化，并参与癫痫发生过程中的基因表达调控。然而，特定脑区 CtBP 家族成员的表达模式及其在神经元内的亚细胞定位在很大程度上尚不清楚。在这里，我们使用特异性抗体在微观和超微结构水平上对 CtBP1 和 CtBP2 在小鼠脑中的表达进行了全面评估。我们对含有细胞核或突触区室的生化分离脑部分中这两种 CtBP 的表达水平进行了定量和比较。我们的研究表明，两种 CtBP 家族成员在脑中具有不同的区域和亚细胞表达模式，并揭示了 CtBP2 在特定脑区中以前未知的突触定位。最后，我们提出了其剪接变体 CtBP2-S 和 CtBP2-L 在神经元中差异化的突触-核靶向的机制。
