Trafficking and Membrane Organization of GPI-Anchored Proteins in Health and Diseases

Curr Top Membr. 2015:75:269-303. doi: 10.1016/bs.ctm.2015.03.006. Epub 2015 Apr 15.

Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a class of lipid-anchored proteins attached to the membranes by a glycolipid anchor that is added, as posttranslation modification, in the endoplasmic reticulum. GPI-APs are expressed at the cell surface of eukaryotes where they play diverse vital functions. Like all plasma membrane proteins, GPI-APs must be correctly sorted along the different steps of the secretory pathway to their final destination. The presence of both a glycolipid anchor and a protein portion confers special trafficking features to GPI-APs. Here, we discuss the recent advances in the field of GPI-AP trafficking, focusing on the mechanisms regulating their biosynthetic pathway and plasma membrane organization. We also discuss how alterations of these mechanisms can result in different diseases. Finally, we will examine the strict relationship between the trafficking and function of GPI-APs in epithelial cells.

Keywords: Cholesterol; Clustering; Epithelial cells; GPI-anchored proteins; Lipid rafts; Membrane trafficking; Oligomerization; Plasma membrane organization; Polarized sorting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / metabolism*
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Embryonic Development / genetics
  • Endoplasmic Reticulum / metabolism
  • Epithelial Cells / metabolism
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism*
  • Glycosylphosphatidylinositols / metabolism
  • Golgi Apparatus / metabolism
  • Hemoglobinuria, Paroxysmal / genetics
  • Hemoglobinuria, Paroxysmal / metabolism*
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / metabolism*
  • Membrane Microdomains / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Phosphorus Metabolism Disorders / genetics
  • Phosphorus Metabolism Disorders / metabolism*
  • Protein Transport

Substances

  • GPI-Linked Proteins
  • Glycosylphosphatidylinositols

Supplementary concepts

  • Hyperphosphatasia with Mental Retardation