Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila.
Essential Function of the Serine Hydroxymethyl Transferase (SHMT) Gene During Rapid Syncytial Cell Cycles in Drosophila.
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DOI：
10.1534/g3.117.043133
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发表时间：
2017-07-05
期刊：
影响因子：
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通讯作者：
Großhans J
中科院分区：
文献类型：
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作者：
Winkler F;Kriebel M;Clever M;Gröning S;Großhans J
许多代谢酶在进化上是高度保守的，在细胞的代谢和生长中起着中心作用。丝氨酸羟甲基转移酶（SHMT）催化丝氨酸和甘氨酸的转化，反之亦然，进入四氢叶酸（THF）介导的C1代谢。我们在胚盘突变体的筛选中鉴定了果蝇SHMT（CG3011）突变。来自SHMT突变体生殖系克隆的胚胎特异性地在囊胚中期转变（MBT）时和细胞化之前将细胞周期阻滞在间期13。该表型是由于酶活性的丧失，因为它不能被催化中心具有点突变的等位基因拯救，而是被基于来自大肠杆菌的SHMT编码序列的等位基因拯救。在SHMT突变胚胎中合子基因表达和母体RNA降解的开始与野生型胚胎中的情况基本相似。SHMT突变体中缺陷的具体时间表明，如果不是由胚胎产生，则至少有一种SHMT依赖性代谢物在间期13中成为限制性的。我们的数据表明，突变的鸡蛋含有母亲提供的和SHMT依赖的代谢物的量，足以早期发展，直到间期13。
Many metabolic enzymes are evolutionarily highly conserved and serve a central function in the catabolism and anabolism of cells. The serine hydroxymethyl transferase (SHMT) catalyzing the conversion of serine and glycine and vice versa feeds into tetrahydrofolate (THF)-mediated C1 metabolism. We identified a Drosophila mutation in SHMT (CG3011) in a screen for blastoderm mutants. Embryos from SHMT mutant germline clones specifically arrest the cell cycle in interphase 13 at the time of the midblastula transition (MBT) and prior to cellularization. The phenotype is due to a loss of enzymatic activity as it cannot be rescued by an allele with a point mutation in the catalytic center but by an allele based on the SHMT coding sequence from Escherichia coli. The onset of zygotic gene expression and degradation of maternal RNAs in SHMT mutant embryos are largely similar to that in wild-type embryos. The specific timing of the defects in SHMT mutants indicates that at least one of the SHMT-dependent metabolites becomes limiting in interphase 13, if it is not produced by the embryo. Our data suggest that mutant eggs contain maternally-provided and SHMT-dependent metabolites in amounts that suffice for early development until interphase 13.