Glycome Atlas
process
Also known as GPI anchoring, glypiation, glycosylphosphatidylinositol anchor
GlcN (α1-6) → Ins; Man (α1-4) → GlcN; Man (α1-6) → Man; Man (α1-2) → Man
How to read these diagrams (SNFG)
Each shape is a class of sugar and each colour a specific one. Structures read right to left, with the reducing end (the point of attachment) on the right.
Plain-language answer
GPI anchoring, also called glypiation, is a way cells attach certain proteins to the outside of the cell using a special sugar-and-fat tag instead of threading the protein through the membrane. The tag is built ahead of time, and an enzyme swaps it onto the end of the protein, letting the fatty part sit in the membrane like a buoy holding the protein at the surface.1
Many important surface proteins are held on by GPI anchors, and this attachment lets them cluster in specific membrane regions and be released when needed. When cells cannot make these anchors properly, the result is serious disease, showing how essential this quiet step of glycosylation is.1
Technical detail
GPI anchoring (glypiation) is the enzyme-directed, post-translational attachment of proteins to a preassembled glycosylphosphatidylinositol glycolipid via the GPI transamidase complex, which cleaves a C-terminal GPI signal sequence and links the exposed carboxyl to the anchor, tethering the protein to the outer leaflet of the plasma membrane.1
The GPI anchor is assembled stepwise on the endoplasmic reticulum membrane as a complete precursor built on a conserved core of phosphatidylinositol, glucosamine, and a mannose-containing glycan terminating in phosphoethanolamine. Proteins destined for anchoring carry a C-terminal GPI signal sequence that is recognized and cleaved by the GPI transamidase complex, which simultaneously forms an amide bond between the new C-terminus and the anchor. This coupled cleavage and attachment is the defining reaction of glypiation.1
After attachment the anchor undergoes lipid and glycan remodeling as the protein moves through the secretory pathway to the cell surface. Because the protein is held only by the lipid moiety in the outer leaflet, GPI-anchored proteins partition into ordered membrane microdomains and can be selectively released by phospholipases, giving cells a way to display and shed these proteins without transmembrane domains.1
Human relevance
Acquired failure to synthesize GPI anchors, through mutation of an early biosynthetic gene, removes protective GPI-anchored proteins from blood cell surfaces and causes paroxysmal nocturnal hemoglobinuria, illustrating the physiological importance of the pathway.1
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References