Sorting of GPI-anchored proteins into ER exit sites by p24 proteins is dependent on remodeled GPI

J Cell Biol. 2011 Jul 11;194(1):61-75. doi: 10.1083/jcb.201012074. Epub 2011 Jul 4.

Abstract

Glycosylphosphatidylinositol (GPI) anchoring of proteins is a posttranslational modification occurring in the endoplasmic reticulum (ER). After GPI attachment, proteins are transported by coat protein complex II (COPII)-coated vesicles from the ER. Because GPI-anchored proteins (GPI-APs) are localized in the lumen, they cannot interact with cytosolic COPII components directly. Receptors that link GPI-APs to COPII are thought to be involved in efficient packaging of GPI-APs into vesicles; however, mechanisms of GPI-AP sorting are not well understood. Here we describe two remodeling reactions for GPI anchors, mediated by PGAP1 and PGAP5, which were required for sorting of GPI-APs to ER exit sites. The p24 family of proteins recognized the remodeled GPI-APs and sorted them into COPII vesicles. Association of p24 proteins with GPI-APs was pH dependent, which suggests that they bind in the ER and dissociate in post-ER acidic compartments. Our results indicate that p24 complexes act as cargo receptors for correctly remodeled GPI-APs to be sorted into COPII vesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • CHO Cells
  • Cells, Cultured
  • Cricetinae
  • Cricetulus
  • Endoplasmic Reticulum / metabolism*
  • GPI-Linked Proteins / metabolism*
  • Glycosylphosphatidylinositols / metabolism*
  • Models, Biological*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vesicular Transport Proteins / metabolism*

Substances

  • GPI-Linked Proteins
  • Glycosylphosphatidylinositols
  • Vesicular Transport Proteins