Organization of GPI-anchored proteins at the cell surface and its physiopathological relevance

Abstract

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a class of proteins attached to the extracellular leaflet of the plasma membrane via a post-translational modification, the glycolipid anchor. The presence of both glycolipid anchor and protein portion confers them unique features. GPI-APs are expressed in all eukaryotes, from fungi to plants and animals. They display very diverse functions ranging from enzymatic activity, signaling, cell adhesion, cell wall metabolism, neuritogenesis, and immune response. Likewise other plasma membrane proteins, the spatio-temporal organization of GPI-APs is critical for their biological activities in physiological conditions. In this review, we will summarize the latest findings on plasma membrane organization of GPI-APs and the mechanism of its regulation in different cell types. We will also examine the involvement of specific GPI-APs namely the prion protein PrP^C, the Folate Receptor alpha and the urokinase plasminogen activator receptor in human diseases focusing on neurodegenerative diseases and cancer.

Keywords:

• GPI-anchored proteins
• clustering
• membrane organization
• cholesterol
• protein trafficking and sorting
• actin cytoskeleton
• membrane domains
• epithelial cell polarity

Acknowledgements

We would like to thank Dr. N. Sauvonnet (Institut Pasteur) for fruitful discussion.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work is supported by Institut Pasteur-Institut Curie PIC3i, and by research grants from Agence Nationale de la Recherche [ANR-16-CE16–0019-01] and Equipe Fondation Recherche Médicale 2014 [DEQ20140329557] to C.Z.