HpSumf1 is involved in the activation of sulfatases responsible for regulation of skeletogenesis during sea urchin development
HpSumf1 is involved in the activation of sulfatases responsible for regulation of skeletogenesis during sea urchin development
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HpSumf1 参与硫酸酯酶的激活，负责海胆发育过程中骨骼形成的调节
DOI：
10.1007/s00427-011-0368-2
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发表时间：
2011
影响因子：
2.4
通讯作者：
山本卓
中科院分区：
文献类型：
--
作者：
佐久間哲史;大西和也;藤田和将;落合博;坂本尚昭;山本卓
在海胆发育过程中，硫酸酯酶如芳基硫酸酯酶和6-O-乙酰肝素硫酸酯酶在形态发生中起着重要的作用。为了激活这些硫酸酯酶，需要硫酸酯酶修饰因子(SUMF)形成Cα-甲酰甘氨酸。在本研究中，为了阐明海胆发育过程中硫酸酯酶激活的调控机制，我们研究了Sumf1和Sumf2的粉状半球藻同系物(分别为HpSumf1和HpSumf2)的表达和功能。在发育早期，HpSumf1mRNA的表达动态变化，而HpSumf2mRNA的表达没有动态变化。利用表达小鼠ARSA的HEK293T细胞对重组HpSumf1和HpSumf2进行的功能分析表明，HpSumf1和HpSumf2均能激活哺乳动物ARSA。用吗啡诺反义寡核苷酸敲除HpSumf1基因可引起海胆胚胎毛刺的异常形成。注射HpSumf2m RNA对骨骼发育无影响，而注射HpSumf1m RNA可引起严重的多毛刺形成。综上所述，这些发现表明HpSumf1参与了控制骨骼形成所需的硫酸酯酶的激活。
Sulfatases such as arylsulfatase and heparan sulfate 6-O-endosulfatase play important roles in morphogenesis during sea urchin development. For the activation of these sulfatases, Cα-formylglycine formation by sulfatase modifying factor (Sumf) is required. In this study, to clarify the regulatory mechanisms for the activation of sulfatases during sea urchin development, we examined the expression and function of theHemicentrotus pulcherrimushomologs of Sumf1 and Sumf2 (HpSumf1 and HpSumf2, respectively). Expression ofHpSumf1but notHpSumf2mRNA was dynamically changed during early development. Functional analyses of recombinant HpSumf1 and HpSumf2 using HEK293T cells expressing mouse arylsulfatase A (ArsA) indicated that HpSumf1 and HpSumf2 were both able to activate mammalian ArsA. Knockdown ofHpSumf1using morpholino antisense oligonucleotides caused abnormal spicule formation in the sea urchin embryo. Injection ofHpSumf2mRNA had no effect on skeletogenesis, while injection ofHpSumf1mRNA induced severe supernumerary spicule formation. Taken together, these findings suggest that HpSumf1 is involved in the activation of sulfatases required for control of skeletogenesis.