Cryptic peroxisomal targeting via alternative splicing and stop codon read-through in fungi
Cryptic peroxisomal targeting via alternative splicing and stop codon read-through in fungi
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DOI：
10.1038/nature11051
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发表时间：
2012-05-24
期刊：
影响因子：
64.8
通讯作者：
Boelker, Michael
中科院分区：
文献类型：
--
作者：
Freitag, Johannes;Ast, Julia;Boelker, Michael
过氧化物酶体是真核细胞器，对长链脂肪酸的代谢很重要（1，2）。在这里，我们表明，在许多真菌物种，糖酵解的几个核心酶，包括甘油醛-3-磷酸脱氢酶（GAPDH）和3-磷酸甘油酸激酶（PGK），驻留在细胞质和过氧化物酶体。我们在这些酶中检测到隐藏的1型过氧化物酶体靶向信号（PTS 1）（3），其通过转录后过程激活。值得注意的是，产生过氧化物酶体同种型的分子机制在不同物种之间差异很大。在担子菌植物病原体玉米黑粉菌中，过氧化物酶体靶向Pgk 1是由核糖体通读引起的，而选择性剪接产生Gapdh的PTS 1。在丝状子囊菌构巢曲霉中，这些酶的过氧化物酶体靶向通过完全相反的机制实现。我们还检测到PTS 1基序的糖酵解酶磷酸丙糖异构酶和果糖二磷酸醛缩酶。联合缺乏过氧化物酶体同工型Gapdh或Pgk 1的玉米突变体表现出降低的毒性。此外，突变分析表明，GAPDH，与其他过氧化物酶体NADH依赖性脱氢酶，在氧化还原稳态的作用。由于其隐藏的性质，部分过氧化物酶体靶向研究细胞质酶仍然未被发现。因此，我们预计，其他真正的细胞质蛋白表现出类似的双重靶向。
Peroxisomes are eukaryotic organelles important for the metabolism of long-chain fatty acids(1,2). Here we show that in numerous fungal species, several core enzymes of glycolysis, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and 3-phosphoglycerate kinase (PGK), reside in both the cytoplasm and peroxisomes. We detected in these enzymes cryptic type 1 peroxisomal targeting signals (PTS1)(3), which are activated by post-transcriptional processes. Notably, the molecular mechanisms that generate the peroxisomal isoforms vary considerably among different species. In the basidiomycete plant pathogen Ustilago maydis, peroxisomal targeting of Pgk1 results from ribosomal read-through, whereas alternative splicing generates the PTS1 of Gapdh. In the filamentous ascomycete Aspergillus nidulans, peroxisomal targeting of these enzymes is achieved by exactly the opposite mechanisms. We also detected PTS1 motifs in the glycolytic enzymes triose-phosphate isomerase and fructose-bisphosphate aldolase. U. maydis mutants lacking the peroxisomal isoforms of Gapdh or Pgk1 showed reduced virulence. In addition, mutational analysis suggests that GAPDH, together with other peroxisomal NADH-dependent dehydrogenases, has a role in redox homeostasis. Owing to its hidden nature, partial peroxisomal targeting of well-studied cytoplasmic enzymes has remained undetected. Thus, we anticipate that further bona fide cytoplasmic proteins exhibit similar dual targeting.