Isolation and characterization of Xenopus laevis homologs of the mouse inv gene and functional analysis of the conserved calmodulin binding sites

Isolation and characterization of Xenopus laevis homologs of the mouse inv gene and functional analysis of the conserved calmodulin binding sites
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小鼠 inv 基因的非洲爪蟾同源物的分离和表征以及保守的钙调蛋白结合位点的功能分析

DOI:
10.1038/sj.cr.7310044
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发表时间:
2006
期刊:
影响因子:
44.1
通讯作者:
T. Yokoyama
T. Yokoyama
中科院分区:
生物学1区
文献类型:
--
作者:
Y. Yasuhiko;K. Shiokawa;T. Mochizuki;M. Asashima;T. Yokoyama

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纯合子inv(胚胎翻转倒置)突变小鼠表现出原位倒置和多囊肾病,这两种疾病都是由于inv基因的缺乏。在此之前,我们建议,inv可能是重要的左右轴的形成,不仅在小鼠,但也在非洲爪蟾,钙调蛋白调节这种inv蛋白的功能。在这里,我们分离并表征了两个非洲爪蟾同源物(Xinv-1和Xinv-2)的小鼠inv基因,并进行了功能分析的保守的IQ图案与钙调素相互作用。Xinv-1在发育早期以与小鼠inv相同的方式表达。出乎意料的是,全长非洲爪蟾inv mRNA注射到非洲爪蟾胚胎,这是从小鼠inv mRNA不同,没有随机化心脏的方向。与小鼠inv mRNA相反,具有突变IQ的爪蟾inv mRNA随机化心脏定向。目前的研究表明,钙调素结合位点(IQ基序)是至关重要的控制小鼠和非洲爪蟾inv蛋白的生物活性。虽然小鼠和非洲爪蟾inv基因具有非常相似的结构,但非洲爪蟾inv和小鼠inv蛋白与钙调素和IQ基序的相互作用可能以不同的方式调节其功能。
The homozygous inv (inversion of embryonic turning) mouse mutant shows situs inversus and polycystic kidney disease, both of which result from the lack of the inv gene. Previously, we suggested that inv may be important for the left–right axis formation, not only in mice but also in Xenopus, and that calmodulin regulates this inv protein function. Here, we isolated and characterized two Xenopus laevis homologs (Xinv-1 and Xinv-2) of the mouse inv gene, and performed functional analysis of the conserved IQ motifs that interact with calmodulin. Xinv-1 expresses early in development in the same manner as mouse inv does. Unexpectedly, a full-length Xenopus inv mRNA did not randomize cardiac orientation when injected into Xenopus embryos, which is different from mouse inv mRNA. Contrary to mouse inv mRNA, Xenopus inv mRNA with mutated IQ randomized cardiac orientation. The present study indicates that calmodulin binding sites (IQ motifs) are crucial in controlling the biological activity of both mouse and Xenopus inv proteins. Although mouse and Xenopus inv genes have a quite similar structure, the interaction with calmodulin and IQ motifs of Xenopus inv and mouse inv proteins may regulate their function in different ways.
DOI: 10.1126/science.8480178
发表时间: 1993-04-30
期刊: SCIENCE
影响因子: 56.9
作者:
YOKOYAMA, T;COPELAND, NG;OVERBEEK, PA
通讯作者: OVERBEEK, PA