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

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

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Membrane / genetics
  • Cell Membrane / metabolism*
  • Endosomes / genetics
  • Endosomes / metabolism
  • Golgi Apparatus / genetics
  • Golgi Apparatus / metabolism*
  • Humans
  • Protein Transport
  • Proteins / genetics
  • Proteins / metabolism*
  • Sorting Nexins / genetics
  • Sorting Nexins / metabolism*
  • Wiskott-Aldrich Syndrome Protein / genetics
  • Wiskott-Aldrich Syndrome Protein / metabolism

Substances

  • Proteins
  • SNX27 protein, human
  • Sorting Nexins
  • WAS protein, human
  • WASHC2C protein, human
  • Wiskott-Aldrich Syndrome Protein