Cellular functions of a cytosolic glycerophosphocholine phosphodiesterase GDE5

我们先前已经证明GDE5是一种胞浆型甘油磷胆碱(GPC)磷酸二酯酶。在这里，我们研究了GDE5在脂肪细胞中的细胞功能，因为GDE5在3T3-L1脂肪细胞分化过程中高表达。在3T3-L1脂肪细胞中，内源性GDE5的敲除意外地显著抑制了脂肪细胞的分化，这是通过调节有丝分裂克隆扩张来实现的。GDE5丰度降低导致细胞内GPC水平显著升高。我们发现，降低GDE5的表达显著上调了3T3-L1细胞中LUMICAN和Decorin等蛋白多糖的mRNA表达。这些结果表明，GDE5丰度降低导致细胞内GPC蓄积导致渗透失衡，抑制了脂肪细胞有丝分裂的克隆性扩张。这些结果揭示了GDE5在渗透平衡中的新作用，渗透平衡依赖于GPC的磷酸二酯酶活性。

We previously showed that GDE5 is a cytosolic glycerophosphocholine (GPC) phosphodiesterase. Here, we characterized the cellular functions of GDE5 in adipocytes because GDE5 expression is highly expressed during 3T3-L1 adipocyte differentiation. Knockdown of endogenous GDE5 in 3T3-L1 adipocytes dramatically suppressed adipocye differentiation, unexpectedly, through a modulation of the mitotic clonal expansion. Decreasing GDE5 abundance resulted in a marked increase in intracellular GPC level. We showed that decreasing GDE5 expression significantly upregulated mRNA expression of proteoglycans such as lumican, and decorin in 3T3-L1 cells. These results suggest that decreasing GDE5 abundance caused osmotic imbalance by the intracellular GPC accumulation and inhibited the mitotic clonal expansion of adipocytes. These provide an insight into the novel roles of GDE5 in osmotic balance which depends on GPC phosphodiesterase activity.