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Nat Commun. 2016 Mar 9;7:10939. doi: 10.1038/ncomms10939.

FAM21 directs SNX27-retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus.

Author information

1
Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
2
Department of Biomedical Sciences, Ajou University School of Medicine, Suwon 443-380, Korea.
3
Department of Brain Science, Ajou University School of Medicine, Suwon 443-380, Korea.
4
Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 443-380, Korea.

Abstract

The endosomal network maintains cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Retromer organizes the endosomal sorting pathway in conjunction with various sorting nexin (SNX) proteins. The SNX27-retromer complex has recently been identified as a major endosomal hub that regulates endosome-to-plasma membrane recycling by preventing lysosomal entry of cargoes. Here, we show that SNX27 directly interacts with FAM21, which also binds retromer, within the Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex. This interaction is required for the precise localization of SNX27 at an endosomal subdomain as well as for recycling of SNX27-retromer cargoes. Furthermore, FAM21 prevents cargo transport to the Golgi apparatus by controlling levels of phosphatidylinositol 4-phosphate, which facilitates cargo dissociation at the Golgi. Together, our results demonstrate that the SNX27-retromer-WASH complex directs cargoes to the plasma membrane by blocking their transport to lysosomes and the Golgi.

PMID:
26956659
PMCID:
PMC4786876
DOI:
10.1038/ncomms10939
[Indexed for MEDLINE]
Free PMC Article

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