Yeditepe University, Biotechnology Graduate Program, Institute of Science and Engineering, Kayisdagi, Istanbul, Turkey; Gebze Technical University, Institute of Biotechnology, 41400, Gebze Kocaeli, Turkey.
University Paris-Saclay, CNRS, Paris Saclay Neuroscience Institute, University Paris-Sud, Orsay, France.
Neurosci Lett. 2020 Nov 1;738:135348. doi: 10.1016/j.neulet.2020.135348. Epub 2020 Sep 3.
Pea3 proteins belong to a subfamily of the E-twentysix (ETS) domain superfamily of transcription factors, which play various roles during development. Polyoma Enhancer-Activator 3 (Pea3) proteins Pea3, ERM and Er81 are particularly involved in tissues with branching morphogenesis, including kidney, lung, mammary gland and nervous system development. A recent transcriptomic study on novel targets of Pea3 transcription factor revealed various axon guidance and nervous system development related targets, supporting a role of Pea3 proteins in motor neuron connectivity, as well as novel targets in signaling pathways involved in synaptic plasticity. This study focuses on the expression of Pea3 family members in hippocampal neurons, and regulation of putative Pea3 targets in Pea3-overexpressing cell lines and following induction of long-term potentiation or seizure in vivo. We show that Pea3 proteins are expressed in hippocampus in both neuronal and non-neuronal cells, and that Pea3 represses Elk-1 but activates Prkca and Nrcam expression in hippocampal cell lines. We also show that mRNA and protein levels of Pea3 family members are differentially regulated in the dentate gyrus and CA1 region upon MECS stimulation, but not upon LTP induction.
豌豆 3 蛋白属于 E-twentysix（ETS）结构域转录因子超家族的一个亚家族，在发育过程中发挥多种作用。多瘤增强子激活因子 3（Pea3）蛋白 Pea3、ERM 和 Er81 特别参与具有分支形态发生的组织，包括肾脏、肺、乳腺和神经系统发育。最近对 Pea3 转录因子的新靶标进行的转录组学研究揭示了各种轴突导向和神经系统发育相关靶标，支持 Pea3 蛋白在运动神经元连接中的作用，以及涉及突触可塑性的信号通路中的新靶标。本研究重点研究了 Pea3 家族成员在海马神经元中的表达，以及在 Pea3 过表达细胞系中的假定 Pea3 靶标和体内长时程增强或癫痫发作后的调节。我们表明 Pea3 蛋白在神经元和非神经元细胞中均在海马体中表达，并且 Pea3 抑制 Elk-1 但激活 Prkca 和 Nrcam 在海马细胞系中的表达。我们还表明，在 MECS 刺激后，齿状回和 CA1 区的 Pea3 家族成员的 mRNA 和蛋白水平差异调节，但在 LTP 诱导后则没有。
