Genetic evidence for a mammalian retromer complex containing sorting nexins 1 and 2
Genetic evidence for a mammalian retromer complex containing sorting nexins 1 and 2
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DOI：
10.1073/pnas.0409558102
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发表时间：
2005-10-18
影响因子：
11.1
通讯作者：
Magnuson, T
中科院分区：
文献类型：
--
作者：
Griffin, CT;Trejo, J;Magnuson, T
我们之前已经证明，假设的哺乳动物反转录成分分类连接蛋白1和2 （Snx1和Snx2）在小鼠中同时被靶向删除时会导致胚胎致死，而其他人已经表明，另一种反转录成分H β 58（也称为mVps26）在被靶向删除时会导致类似的致死。在目前的研究中，我们在小鼠中解决了这些哺乳动物逆转录成分的遗传相互作用。我们的研究结果揭示了H β 58、SNX1和SNX2之间的功能相互作用，并强烈表明在胚胎发育过程中，SNX2比SNX1在逆转录酶活性中发挥更关键的作用。这一遗传证据支持含有SNX1和SNX2的哺乳动物反转录复合物的存在，并确定SNX2是反转录生物学的重要介质。此外，我们发现含有SNX1和SNX2的哺乳动物逆转录复合物在胚胎发育中具有重要作用，不依赖于阳离子依赖性甘露糖6-磷酸受体的转运。
We have previously shown that the putative mammalian retromer components sorting nexins 1 and 2 (Snx1 and Snx2) result in embryonic lethality when simultaneously targeted for deletion in mice, whereas others have shown that H beta 58 (also known as mVps26), another retromer component, results in similar lethality when targeted for deletion. In the current study, we address the genetic interaction of these mammalian retromer components in mice. Our findings reveal a functional interaction between H beta 58, SNX1, and SNX2 and strongly suggest that SNX2 plays a more critical role than SNX1 in retromer activity during embryonic development. This genetic evidence supports the existence of mammalian retromer complexes containing SNX1 and SNX2 and identifies SNX2 as an important mediator of retromer biology. Moreover, we find that mammalian retromer complexes containing SNX1 and SNX2 have an essential role in embryonic development that is independent of cation-independent mannose 6-phosphate receptor trafficking.