GPI Anchoring

GPI anchoring is a post-translational modification (PTM) of proteins with a glycolipid that allows the attachment of specific proteins to the cell membrane. This process is crucial for maintaining the integrity and functionality of cells. Many important proteins, such as cell surface receptors (folate receptors, GDNF receptor alphas, FcγRIIIb, and others), enzymes (alkaline phosphatases (ALPs), 5'-nucleotidase, dipeptidase, and others), and adhesion molecules (contactins, glypicans, CD48, and others), rely on GPI anchoring for their proper localization and activity.

Figure 1. Schematic representation of a GPI-anchored protein.
(Source: Boes, D. M. et al., 2021)

Introduction to GPI

Glycosylphosphatidylinositol (GPI) is a complex glycolipid composed of mannoses (Mans), glucosamine, ethanolamine phosphate (EtNP), and inositol phospholipids. It can be covalently linked to the carboxyl terminus of certain proteins, anchoring them to the outer leaflet of the cell plasma membrane to perform biological functions. These proteins are known as GPI-anchored proteins (GPI-APs). In the human body, at least 150 proteins have been identified as GPI-anchored proteins, which are widely distributed in various cell types. These GPI-anchored proteins are involved in many biological processes, including membrane-associated enzyme activities (PLAP, Phospholipase B, Aspartic proteinase, etc.), cell signal transduction (CD55, CD59 and calcium channel regulatory subunit a2d1, etc.), cell adhesion (OPCML, CD56, etc.) and antigen presentation (Thy-1, CD14, CD52, etc.), etc. Aberrations in the biosynthesis of GPI-anchored proteins commonly lead to various diseases, such as paroxysmal nocturnal hemoglobinuria, intellectual disabilities, and epileptic seizures.

Cleavage of GPI Anchoring

Cleavage of the GPI-anchor is an essential step in the processing of GPI-anchored proteins. This process involves the removal of the GPI-anchor from the protein, releasing it from the cell membrane. One of the enzymes responsible for this cleavage is phospholipase C (PLC). PLC recognizes and cleaves the GPI anchor at specific sites, resulting in the release of the protein. This cleavage event allows the protein to be released into the extracellular environment or to undergo further processing within the cell. The exact mechanism and regulation of GPI-anchor cleavage are still areas of active research.

The cleavage of GPI-anchored proteins is a tightly controlled process with important implications for cellular function. The release of GPI-anchored proteins from the cell membrane can have significant effects on cell signaling, cell adhesion, and other biological processes in which these proteins are involved.

For example, in the immune system, the cleavage of GPI-anchored complement regulatory proteins such as decay-accelerating factor (DAF) and CD59 from the cell surface is crucial for their ability to regulate the complement system. By cleaving these GPI-anchored proteins, the complement system can be regulated effectively, preventing excessive activation and damage to the host cells. Additionally, the cleavage of GPI-anchored proteins can be regulated in response to various stimuli, allowing for dynamic control of their release. For instance, in certain immune cells, the cleavage of GPI-anchored proteins can be modulated by signaling pathways activated during inflammation or immune responses.

For research use only, not for use in diagnostic procedures.

GPI Anchoring-Related Antibodies

GPI Anchoring-Related Antigens

GPI Anchoring-Related ELISA Kits