rSac3, a novel Sac domain phosphoinositide phosphatase, promotes neurite outgrowth in PC12 cells.
rSac3, a novel Sac domain phosphoinositide phosphatase, promotes neurite outgrowth in PC12 cells.
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rSac3 是一种新型 Sac 结构域磷酸肌醇磷酸酶，可促进 PC12 细胞中的神经突生长。
DOI：
10.1038/cr.2007.82
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发表时间：
2007
期刊：
影响因子：
44.1
通讯作者：
Jing,Naihe
中科院分区：
文献类型：
--
作者：
Yuan,Yiyuan;Gao,Xiang;Guo,Ning;Zhang,Hui;Xie,Zhiqin;Jin,Meilei;Li,Baoming;Yu,Lei;Jing,Naihe
SAC结构域蛋白属于一个新发现的磷脂酰肌醇磷酸酶家族(PIPPase家族)。尽管这个哺乳动物SAC结构域的PIPPase家族具有很好的酶活性，但其生物学功能在很大程度上仍不清楚。我们发现了一个新的含有SAC结构域的蛋白--大鼠Sac3(RSac3)，它广泛表达于多种组织中，并定位于内质网、高尔基复合体和循环内小体。RSac3在体外显示以PI(3)P、PI(4)P和PI(3，5)P2为底物的PIPPase活性，SAC结构域催化核心的突变使其酶活性丧失。在神经生长因子(NGF)刺激的PC12细胞神经分化过程中，rSac3的表达上调，该蛋白的过度表达促进了PC12细胞突起的生长。相反，反义寡核苷酸抑制rSac3的表达可以减少NGF刺激的PC12细胞的突起生长，rSac3的活性位点突变消除了其促进突起生长的活性。这些结果表明，rSac3通过其PIPPase活性促进神经突起的生长，提示SAC域PIPPase蛋白可能参与了内质网和高尔基复合体向质膜的正向转运，并可能作为这一重要的神经细胞生长和分化过程的调节因子。
Sac domain-containing proteins belong to a newly identified family of phosphoinositide phosphatases (the PIPPase family). Despite well-characterized enzymatic activity, the biological functions of this mammalian Sac domain PIPPase family remain largely unknown. We identified a novel Sac domain-containing protein, rat Sac3 (rSac3), which is widely expressed in various tissues and localized to the endoplasmic reticulum, Golgi complex and recycling endosomes. rSac3 displays PIPPase activity with PI (3) P, PI (4) P and PI (3, 5) P 2 as substrates in vitro, and a mutation in the catalytic core of the Sac domain abolishes its enzymatic activity. The expression of rSac3 is upregulated during nerve growth factor (NGF)-stimulated PC12 cell neuronal differentiation, and overexpression of this protein promotes neurite outgrowth in PC12 cells. Conversely, inhibition of rSac3 expression by antisense oligonucleotides reduces neurite outgrowth of NGF-stimulated PC12 cells, and the active site mutation of rSac3 eliminates its neurite-outgrowth-promoting activity. These results indicate that rSac3 promotes neurite outgrowth in differentiating neurons through its PIPPase activity, suggesting that Sac domain PIPPase proteins may participate in forward membrane trafficking from the endoplasmic reticulum and Golgi complex to the plasma membrane, and may function as regulators of this crucial process of neuronal cell growth and differentiation.