Shukla Sushmita, Pillai Anoop Narayana, Rahaman Abdur
National Institute of Science Education and Research (NISER), Bhubaneswar, HBNI, P.O. Jatni, Khurda, Odisha 752 050, India.
J Biosci. 2018 Sep;43(4):693-706.
Nuclear envelope morphology protein 1 along with a phosphatidate phosphatase regulates lipid homeostasis and membrane biogenesis in yeast and mammals. We investigated four putative homologues and ) in the genome. Disruption of or did not compromise normal cell growth. In contrast, we were unable to generate knockout strain of under the same conditions, indicating that is essential for growth. Interestingly, loss of TtNEM1B but not TtNEM1C or TtNEM1D caused a reduction in lipid droplet number. Similar to yeast and mammals, TtNem1B of Tetrahymena exerts its function via Pah1, since we found that PAH1 overexpression rescued loss of Nem1 function. However, unlike NEM1 in other organisms, does not regulate ER/nuclear morphology. Similarly, neither TtNEM1C nor TtNEM1D is required to maintain normal ER morphology. While Tetrahymena PAH1 was shown to functionally replace yeast earlier, we observed that homologues did not functionally replace yeast NEM1. Overall, our results suggest the presence of a conserved cascade for regulation of lipid homeostasis and membrane biogenesis in . Our results also suggest a Nem1-independent function of Pah1 in the regulation of ER morphology in .
核膜形态蛋白1与一种磷脂酸磷酸酶共同调节酵母和哺乳动物中的脂质稳态及膜生物合成。我们在基因组中研究了四个假定的同源物（和）。破坏或不会损害正常细胞生长。相反，在相同条件下我们无法产生基因敲除菌株，这表明对生长至关重要。有趣的是，TtNEM1B的缺失而非TtNEM1C或TtNEM1D的缺失导致脂滴数量减少。与酵母和哺乳动物类似，嗜热四膜虫的TtNem1B通过Pah1发挥其功能，因为我们发现PAH1的过表达挽救了Nem1功能的丧失。然而，与其他生物体中的NEM1不同，不调节内质网/核形态。同样，维持正常内质网形态也不需要TtNEM1C和TtNEM1D。虽然之前已证明嗜热四膜虫的PAH1在功能上可替代酵母，但我们观察到同源物在功能上不能替代酵母NEM1。总体而言，我们的结果表明在中存在一个保守的级联反应来调节脂质稳态和膜生物合成。我们的结果还表明Pah1在中调节内质网形态方面具有不依赖Nem1的功能。
