Divergent evolution of the vertebrate polysialyltransferase Stx and Pst genes revealed by fish-to-mammal comparison.
Divergent evolution of the vertebrate polysialyltransferase Stx and Pst genes revealed by fish-to-mammal comparison.
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DOI：
10.1016/j.ydbio.2007.03.032
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发表时间：
2007-06
影响因子：
2.7
通讯作者：
Monika Marx;Eric Rivera‐Milla;Katharina Stummeyer;R. Gerardy-Schahn;M. Bastmeyer
中科院分区：
文献类型：
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作者：
Monika Marx;Eric Rivera‐Milla;Katharina Stummeyer;R. Gerardy-Schahn;M. Bastmeyer
聚唾液酸(PSA)是一种附着在神经细胞黏附分子(NCAM)上的发育调节碳水化合物。PSA参与细胞迁移、突起生长和神经元可塑性等动态过程。在哺乳动物中，NCAM的聚唾液酸化是由两种聚唾液酸转移酶STX(ST8Sia II)和PST(ST8Sia IV)独立催化的，其中STX主要作用于发育早期，PST主要作用于发育后期和成年期。在这里，我们对斑马鱼STX和PST同源基因在鱼类发育过程中的功能进行了表征，并在体外评估了它们对NCAM的催化亲和力。这两个基因都具有典型的基因结构，并与它们在哺乳动物中的同源基因具有保守的同源性。表达分析、基因靶向敲除实验和体外催化实验表明，斑马鱼STX即使不是唯一的，也是执行NCAM-PSA修饰的主要-如果不是唯一的-在发育中和成年鱼中。STX基因的敲除只影响PSA的合成，导致轴突生长和导向方面的缺陷。斑马鱼PST原则上能够合成PSA，然而，我们的数据反对该酶在发育过程中的基本功能。我们的发现揭示了脊椎动物中STX和PST酶的一个重要差异，这也是脊椎动物中差异基因丢失和PST基因快速进化的特征。
Polysialic acid (PSA) is a developmentally regulated carbohydrate attached to the neural cell adhesion molecule (NCAM). PSA is involved in dynamic processes like cell migration, neurite outgrowth and neuronal plasticity. In mammals, polysialylation of NCAM is catalyzed independently by two polysialyltransferases, STX (ST8Sia II) and PST (ST8Sia IV), with STX mainly acting during early development and PST at later stages and into adulthood. Here, we functionally characterize zebrafish Stx and Pst homolog genes during fish development and evaluate their catalytic affinity for NCAM in vitro. Both genes have the typical gene architecture and share conserved synteny with their mammalian homologues. Expression analysis, gene-targeted knockdown experiments and in vitro catalytic assays indicate that zebrafish Stx is the principal–if not unique–polysialyltransferase performing NCAM-PSA modifications in both developing and adult fish. The knockdown of Stx exclusively affects PSA synthesis, producing defects in axonal growth and guidance. Zebrafish Pst is in principle capable of synthesizing PSA, however, our data argue against a fundamental function of the enzyme during development. Our findings reveal an important divergence of Stx and Pst enzymes in vertebrates, which is also characterized by a differential gene loss and rapid evolution of Pst genes within the bony-fish class.