Genetic evidence for a mammalian retromer complex containing sorting nexins 1 and 2

doi:10.1073/pnas.0409558102

Genetic evidence for a mammalian retromer complex containing sorting nexins 1 and 2

^*Department of Genetics and Carolina Center for Genome Sciences and ^†Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599

Edited by David D. Sabatini, New York University School of Medicine, New York, NY (received for review December 21, 2004)

Abstract

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 Hβ58 (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 Hβ58, 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.

Footnotes

↵ ‡ To whom correspondence should be addressed. E-mail: terry_magnuson{at}med.unc.edu.
Author contributions: C.T.G. and T.M. designed research; C.T.G. performed research; C.T.G. and J.T. contributed new reagents/analytic tools; C.T.G., J.T., and T.M. analyzed data; and C.T.G. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: CI-MPR, cation-independent mannose 6-phosphate receptor; En, embryonic day n; MEF, mouse embryonic fibroblast; RT, reverse transcription; SNX, sorting nexin.