Two isoforms of TALDO1 generated by alternative translational initiation show differential nucleocytoplasmic distribution to regulate the global metabolic network.
Two isoforms of TALDO1 generated by alternative translational initiation show differential nucleocytoplasmic distribution to regulate the global metabolic network.
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DOI：
10.1038/srep34648
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发表时间：
2016-10-05
影响因子：
4.6
通讯作者：
Oka M
中科院分区：
文献类型：
--
作者：
Moriyama T;Tanaka S;Nakayama Y;Fukumoto M;Tsujimura K;Yamada K;Bamba T;Yoneda Y;Fukusaki E;Oka M
转醛醇酶1(TALDO1)是磷酸戊糖途径中的限速酶，传统上认为该途径存在于细胞质中。在这项研究中，我们发现TALDO1基因有两个翻译起始点，产生两种不同的亚型，因为存在前10个N-末端氨基酸。值得注意的是，长的和短的异构体分别差异地定位于细胞核和细胞质。下拉和体外转运分析表明，与短异构体不同，长异构体与Importinα结合，并以依赖Importinα/β的方式主动转运到细胞核中，表明10个N末端氨基酸是其核定位所必需的。此外，我们还发现这两种异构体可以形成具有不同局域动力学的同源和/或异源二聚体。代谢物分析表明，TALDO1的亚细胞定位对其在磷酸戊糖途径中的活性不是至关重要的。然而，这两种异构体的表达不同地影响了不同代谢物的水平，包括三羧酸循环的成分、核苷酸和糖。这些结果表明，TALDO1的核质分布通过交替的翻译起始和二聚体形成而调节，在广泛的代谢网络中发挥着重要作用。
Transaldolase 1 (TALDO1) is a rate-limiting enzyme involved in the pentose phosphate pathway, which is traditionally thought to occur in the cytoplasm. In this study, we found that the gene TALDO1 has two translational initiation sites, generating two isoforms that differ by the presence of the first 10 N-terminal amino acids. Notably, the long and short isoforms were differentially localised to the cell nucleus and cytoplasm, respectively. Pull-down and in vitro transport assays showed that the long isoform, unlike the short one, binds to importin α and is actively transported into the nucleus in an importin α/β-dependent manner, demonstrating that the 10 N-terminal amino acids are essential for its nuclear localisation. Additionally, we found that these two isoforms can form homo- and/or hetero-dimers with different localisation dynamics. A metabolite analysis revealed that the subcellular localisation of TALDO1 is not crucial for its activity in the pentose phosphate pathway. However, the expression of these two isoforms differentially affected the levels of various metabolites, including components of the tricarboxylic acid cycle, nucleotides, and sugars. These results demonstrate that the nucleocytoplasmic distribution of TALDO1, modulated via alternative translational initiation and dimer formation, plays an important role in a wide range of metabolic networks.
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影响因子：
13.8
作者：
Patra, Krushna C.;Hay, Nissim
通讯作者：
Hay, Nissim
影响因子：
4.8
作者：
Banki, K;Hutter, E;Perl, A
通讯作者：
Perl, A
影响因子：
5.3
作者：
Plafker, K;Macara, IG
通讯作者：
Macara, IG
影响因子：
5.4
作者：
CHENIK, M;CHEBLI, K;BLONDEL, D
通讯作者：
BLONDEL, D
DOI：
10.1073/pnas.1207846109
发表时间：
2012-09-11
影响因子：
11.1
作者：
Lee, Sooncheol;Liu, Botao;Qian, Shu-Bing
通讯作者：
Qian, Shu-Bing