Griffin Courtney T, Trejo JoAnn, Magnuson Terry
Department of Genetics and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA.
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15173-7. doi: 10.1073/pnas.0409558102. Epub 2005 Oct 7.
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 Hbeta58 (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 Hbeta58, 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.
我们之前已经表明，假定的哺乳动物逆向转运复合物成分分选连接蛋白1和2（Snx1和Snx2）在小鼠中同时被靶向敲除时会导致胚胎致死，而其他人已经表明，另一种逆向转运复合物成分Hbeta58（也称为mVps26）在被靶向敲除时也会导致类似的致死性。在当前的研究中，我们研究了这些哺乳动物逆向转运复合物成分在小鼠中的遗传相互作用。我们的研究结果揭示了Hbeta58、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在逆向转运复合物活性中比SNX1发挥更关键的作用。这一遗传学证据支持了含有SNX1和SNX2的哺乳动物逆向转运复合物的存在，并将SNX2确定为逆向转运复合物生物学的重要调节因子。此外，我们发现含有SNX1和SNX2的哺乳动物逆向转运复合物在胚胎发育中具有独立于不依赖阳离子的甘露糖6-磷酸受体运输的重要作用。
