The protein transglutaminase 2 (TG2) has been implicated as a modulator of neuronal viability. TG2's role in mediating cell survival processes has been suggested to involve its ability to alter transcriptional events. The goal of this study was to examine the role of TG2 in neuronal survival and to begin to delineate the pathways it regulates. We show that depletion of TG2 significantly compromises the viability of neurons in the absence of any stressors. RNA sequencing revealed that depletion of TG2 dysregulated the expression of 86 genes with 59 of these being upregulated. The genes that were upregulated by TG2 knockdown were primarily involved in extracellular matrix function, cell signaling and cytoskeleton integrity pathways. Finally, depletion of TG2 significantly reduced neurite length. These findings suggest for the first time that TG2 plays a crucial role in mediating neuronal survival through its regulation of genes involved in neurite length and maintenance.

蛋白质转谷氨酰胺酶 2 (TG2) 被认为是神经元活力的调节剂。 TG2 在介导细胞生存过程中的作用被认为涉及其改变转录事件的能力。本研究的目的是检查 TG2 在神经元存活中的作用并开始描绘它调节的途径。我们发现，在没有任何应激源的情况下，TG2 的消耗会显着损害神经元的活力。 RNA测序显示，TG2的缺失导致86个基因的表达失调，其中59个基因表达上调。 TG2 敲低上调的基因主要涉及细胞外基质功能、细胞信号传导和细胞骨架完整性途径。最后，TG2 的消耗显着减少了神经突长度。这些发现首次表明，TG2 通过调节涉及神经突长度和维持的基因，在介导神经元存活中发挥着至关重要的作用。