International Peace Maternity & Child Health Hospital, Shanghai Key laboratory for Embryo-Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Institute of Reproductive Medicine, School of Medicine, Nantong University, Nantong, Jiangsu, China.
Mol Reprod Dev. 2019 Sep;86(9):1199-1209. doi: 10.1002/mrd.23236. Epub 2019 Jul 18.
G kinase-anchoring protein 1 (GKAP1) is a G kinase-associated protein that is conserved in many eutherians and is mainly expressed in the testis, especially in spermatocytes and round spermatids. The function of GKAP1 in the testis is largely unknown. Here, we revealed that deletion of GKAP1 led to an increase in sperm production with swollen epididymis, and germ cell apoptosis was found to decrease in GKAP1 knock-out mice. Further investigations showed that a deficiency of GKAP1 could partly change the cellular location of cGK-Iα and increase the amount of active cAMP response element-binding protein (CREB) in the nucleus. Therefore, the expression of a particular inhibitor of apoptosis proteins (IAPs) was upregulated because of the activation of CREB, and this increase in IAPs was associated with a decrease in the level of activated caspase-3. These results suggest that a deficiency of GKAP1 in mouse testis could increase sperm production through a reduction of the spontaneous apoptosis of germ cells in the testis, possibly because of a change in the activity of the cGK-Iα pathway.
G 激酶锚定蛋白 1（GKAP1）是一种与 G 激酶相关的蛋白，在许多真兽类动物中保守存在，主要在睾丸中表达，特别是在精母细胞和圆形精子细胞中。GKAP1 在睾丸中的功能在很大程度上尚不清楚。在这里，我们揭示了 GKAP1 的缺失导致精子产量增加，附睾肿胀，并且在 GKAP1 敲除小鼠中发现生殖细胞凋亡减少。进一步的研究表明，GKAP1 的缺乏可以部分改变 cGK-Iα 的细胞位置，并增加细胞核中活性 cAMP 反应元件结合蛋白（CREB）的量。因此，由于 CREB 的激活，特定凋亡抑制蛋白（IAPs）的表达上调，而 IAPs 的增加与激活的 caspase-3 水平降低有关。这些结果表明，小鼠睾丸中 GKAP1 的缺乏可以通过减少睾丸中生殖细胞的自发性凋亡来增加精子产量，这可能是由于 cGK-Iα 途径的活性变化所致。
