Rab GTPase regulation of retromer-mediated cargo export during endosome maturation

Mol Biol Cell. 2012 Jul;23(13):2505-15. doi: 10.1091/mbc.E11-11-0915. Epub 2012 May 16.

Abstract

The retromer complex, composed of sorting nexin subunits and a Vps26/Vps29/Vps35 trimer, mediates sorting of retrograde cargo from the endosome to the trans-Golgi network. The retromer trimer subcomplex is an effector of Rab7 (Ypt7 in yeast). Whereas endosome targeting of human retromer has been shown to require Rab7-GTP, targeting of yeast retromer to the endosome is independent of Ypt7-GTP and requires the Vps5 and Vps17 retromer sorting nexin subunits. An evolutionarily conserved amino acid segment within Vps35 is required for Ypt7/Rab7 recognition in vivo by both yeast and human retromer, establishing that Rab recognition is a conserved feature of this subunit. Recognition of Ypt7 by retromer is required for its function in retrograde sorting, and in yeast cells lacking the guanine nucleotide exchange factor for Ypt7, retrograde cargo accumulates in endosomes that are decorated with retromer, revealing an additional role for Rab recognition at the cargo export stage of the retromer functional cycle. In addition, yeast retromer trimer antagonizes Ypt7-regulated organelle tethering and fusion of endosomes/vacuoles via recognition of Ypt7. Thus retromer has dual roles in retrograde cargo export and in controlling the fusion dynamics of the late endovacuolar system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Motifs
  • Endosomes*
  • Humans
  • Intracellular Membranes / metabolism
  • Jurkat Cells
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Secretory Pathway
  • Sequence Deletion
  • Vacuoles / metabolism
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • rab GTP-Binding Proteins / chemistry
  • rab GTP-Binding Proteins / metabolism*

Substances

  • PEP1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • VPS17 protein, S cerevisiae
  • VPS35 protein, S cerevisiae
  • VPS5 protein, S cerevisiae
  • Vesicular Transport Proteins
  • YPT7 protein, S cerevisiae
  • rab GTP-Binding Proteins