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

Lee, Seongju, Chang, Jaerak, Blackstone, Craig·2016·Nature Communications

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.

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  • The WASH complex functions in endocytic recycling, maintenance of endolysosomal network integrity, exocytosis, cell adhesion, and cell migration.

    “The WASH complex functions in the endocytic recycling of various types of membrane proteins, maintenance of endolysosomal network integrity, exocytosis, cell adhesion, and cell migration (11-23).”

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Metadata

Authors
Lee, S., Chang, J., & Blackstone, C.
Venue
Nature Communications
Published
2016-03-09
Volume
7
Issue
1
ISSN
2041-1723
Cited by
73
References
1
Language
en

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