Division of Organelle Homeostasis, Medical Institute of Bioregulation, Kyushu University.
Department of Cell Biology, Johns Hopkins University School of Medicine.
Proc Jpn Acad Ser B Phys Biol Sci. 2019;95(2):75-85. doi: 10.2183/pjab.95.007.
GTP is an essential source of energy that supports a large array of cellular mechanochemical structures ranging from protein synthesis machinery to cytoskeletal apparatus for maintaining the cell cycle. However, GTP regulation during the cell cycle has been difficult to investigate because of heterogenous levels of GTP in asynchronous cell cycles and genetic redundancy of the GTP-generating enzymes. Here, in the unicellular red algae Cyanidioschyzon merolae, we demonstrated that the ATP-GTP-converting enzyme DYNAMO2 is an essential regulator of global GTP levels during the cell cycle. The cell cycle of C. merolae can be highly synchronized by light/dark stimulations to examine GTP levels at desired time points. Importantly, the genome of C. merolae encodes only two isoforms of the ATP-GTP-converting enzyme, namely DYNAMO1 and DYNAMO2. DYNAMO1 regulates organelle divisions, whereas DYNAMO2 is entirely localized in the cytoplasm. DYNAMO2 protein levels increase during the S-M phases, and changes in GTP levels are correlated with these DYNAMO2 protein levels. These results indicate that DYNAMO2 is a potential regulator of global GTP levels during the cell cycle.
GTP 是一种重要的能源来源,支持着从蛋白质合成机制到维持细胞周期的细胞骨架装置等各种细胞机械化学结构。然而,由于细胞周期中 GTP 水平的异质性和产生 GTP 的酶的遗传冗余,细胞周期中的 GTP 调节一直难以研究。在这里,在单细胞红藻 Cyanidioschyzon merolae 中,我们证明了 ATP-GTP 转化酶 DYNAMO2 是细胞周期中全局 GTP 水平的重要调节剂。通过光/暗刺激可以高度同步 C. merolae 的细胞周期,以在所需时间点检查 GTP 水平。重要的是,C. merolae 的基因组仅编码两种 ATP-GTP 转化酶的同工型,即 DYNAMO1 和 DYNAMO2。DYNAMO1 调节细胞器分裂,而 DYNAMO2 则完全定位于细胞质中。DYNAMO2 蛋白水平在 S-M 期增加,GTP 水平的变化与这些 DYNAMO2 蛋白水平相关。这些结果表明 DYNAMO2 是细胞周期中全局 GTP 水平的潜在调节剂。