Mammalian GPI-anchor modifications and the enzymes involved

• Published in: Biochemical Society transactions Vol. 48; no. 3; p. 1129
• Main Authors: Liu, Yi-Shi, Fujita, Morihisa
• Format: Journal Article
• Language: English
• Published: England 30-06-2020
• Subjects: Animals; Cell Membrane - metabolism; Endoplasmic Reticulum - enzymology; Glycosylphosphatidylinositols - biosynthesis; Golgi Apparatus - enzymology; Humans; Male; Membrane Microdomains - enzymology; Membrane Proteins - metabolism; Neurogenesis; Protein Domains; Protein Folding; Protein Transport; Spermatogenesis
• ISSN: 1470-8752
• DOI: 10.1042/bst20191142

Glycosylphosphatidylinositol (GPI) is a glycolipid added to the C-terminus of a large variety of proteins in eukaryotes, thereby anchoring these proteins to the cell surface. More than 150 different human proteins are modified with GPI, and GPI-anchored proteins (GPI-APs) play critical roles in embryogenesis, neurogenesis, immunity, and fertilization. GPI-APs are biosynthesized in the endoplasmic reticulum (ER) and transported to the plasma membrane via the Golgi apparatus. During transport, GPI-APs undergo structural remodeling that is important for the efficient folding and sorting of GPI-APs. Asparagine-linked glycan-dependent folding and deacylation by PGAP1 work together to ensure that correctly folded GPI-APs are transported from the ER to the Golgi. Remodeling of the GPI lipid moiety is critical for the association of GPI-APs with lipid rafts. On the cell surface, certain GPI-APs are cleaved by GPI cleavage enzymes and released from the membrane, a key event in processes such as spermatogenesis and neurogenesis. In this review, we discuss the enzymes involved in GPI-AP biosynthesis and the fate of GPI-APs in mammalian cells, with a focus on the assembly, folding, degradation, and cleavage of GPI-APs.