Genetic evidence for a mammalian retromer complex containing sorting nexins 1 and 2.
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.
Griffin
Courtney T
CT
Department of Genetics and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC 27599, USA.
Trejo
JoAnn
J
Magnuson
Terry
T
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D058305:Sorting Nexins; D015996:Survival Rate; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D015017:Yolk Sac / Q000166:cytology / Q000378:metabolism
D002352:Carrier Proteins; D046912:Multiprotein Complexes; D012333:RNA, Messenger; C505835:SNX1 protein, mouse; C505836:SNX2 protein, mouse; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C089989:Vps26 protein, mouse