Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth. Here, we examined whether RGS5 regulates Shh signaling in neurons. RGS5 transcripts were found to be expressed in cortical neurons and their expression gradually declined in a time-dependent manner in culture system. When an adenovirus expressing RGS5 was introduced into an in vitro cell culture model of cortical neurons, RGS5 overexpression significantly reduced neurite outgrowth and FM4-64 uptake, while cAMP-PKA signaling was also affected. These findings suggest that RGS5 inhibits Shh function during neurite outgrowth and the presynaptic terminals of primary cortical neurons mature via modulation of cAMP.

中文翻译：

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G蛋白信号传导5（RGS5）的调节剂抑制小鼠皮质神经元中的声刺猬功能。

G蛋白信号传导5（RGS5）的调节剂充当Gαi亚基的GTPase激活蛋白（GAP），并负向调节G蛋白偶联的受体信号传导。但是，它的存在和功能在有丝分裂后分化的原代神经元中仍然是未知的。在神经发育过程中，声波刺猬（Shh）信号通过Gαi活性参与细胞信号通路。尤其是，Shh信号对于胚胎神经管构图至关重要，而神经管构图已牵涉到涉及神经突生长的神经元极化。在这里，我们检查了RGS5是否调节神经元中的Shh信号传导。发现RGS5转录物在皮质神经元中表达，并且其表达在培养系统中以时间依赖性的方式逐渐下降。当将表达RGS5的腺病毒引入体外皮层神经元细胞培养模型时，RGS5的过表达显着降低了神经突的长出和FM4-64的摄取，而cAMP-PKA信号也受到影响。这些发现表明，RGS5在神经突生长过程中抑制Shh功能，并且通过调节cAMP使原代皮层神经元的突触前末端成熟。