GPI / GlycosylPhosphatidylInositol acts as a membrane anchor for many cell surface proteins. GPI is synthesized in the endoplasmic reticulum. In humans, a single pathway consisting of nine reactions; appears to be responsible for the synthesis of the major GPI species involved in membrane protein anchoring.
Glycosylphosphatidyl inositol (GPI) in Essentials of Glycobiology
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Biochemistry. 2008 Jul 8;47(27):6991-7000.
The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins.
Paulick MG, Bertozzi CR.
Department of Chemistry, University of California, Berkeley, California 94720, USA.
Positioned at the C-terminus of many eukaryotic proteins, the glycosylphosphatidylinositol (GPI) anchor is a posttranslational modification that anchors the modified protein in the outer leaflet of the cell membrane. The GPI anchor is a complex structure comprising a phosphoethanolamine linker, glycan core, and phospholipid tail. GPI-anchored proteins are structurally and functionally diverse and play vital roles in numerous biological processes. While several GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. This review discusses the structural diversity of the GPI anchor and its putative cellular functions, including involvement in lipid raft partitioning, signal transduction, targeting to the apical membrane, and prion disease pathogenesis. We specifically highlight studies in which chemically synthesized GPI anchors and analogues have been employed to study the roles of this unique posttranslational modification.
phosphatidylinositol phospholipase C (PI-PLC), was found to release from tissues
alkaline phosphatase (APase)
5′-nucleotidase
erythrocyte acetylcholinesterase (AChE),
List of GPI-linked Proteins 2008
In fact, many GPI-anchored proteins can transfer spontaneously to cell membranes both in vitro and in vivo, a process that has been termed “cell surface painting”
The significance of the GPI anchor structure has yet to be deduced . The GPI anchor could have a genuine functional role in some or all anchored proteins, or it could merely be a vestigial relic.
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The only confirmed role of the GPI anchor is to provide the attached protein with a stable membrane anchoring device that is resistant to most extracellular proteases and lipases
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Given that there are many ways in which a protein can be attached to the cell membrane, the GPI anchor is a fairly complicated structure when compared to a simple lipid or transmembrane domain. It is possible that the GPI anchor serves other biological functions besides a membrane anchor.
Many GPI-anchored proteins involved in signaling and cell−cell communication, such as DAF and Thy-1, diffuse freely on the cell surface, allowing these proteins to move rapidly in response to external stimuli
where the membrane is depolarized and forms blebs
he GPI Anchor May Allow for Regulation of Its Associated Protein via Phospholipase Cleavage. The susceptibility of the GPI anchor to cleavage from its associated protein by phospholipases, such as PI-PLC and phopholipase D, has been suggested as a mechanism for the selective regulation of GPI-anchored proteins
Other GPI-anchored proteins, such as NCAM, are involved in cellular adhesion and communication and might benefit from the ability to move rapidly on the cell surface in response to external
stimuli.
Braz J Med Biol Res. 1994 Feb;27(2):297-301.
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The tails of two proteins: the scrapie prion protein and the ciliary neurotrophic factor receptor.
Stahl N, Boulton TG, Ip N, Davis S, Yancopoulos GD.
Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Many proteins with a variety of functions have proven to have glycosylphosphatidylinositol (GPI)-linkages; two members of this family are the scrapie prion protein and the receptor for ciliary neurotrophic factor (CNTF). The scrapie prion protein has two isoforms: PrPC is found in brain cells from normal animals, while PrPSc is an abnormal isoform that is only found in scrapie-infected animals. PrPSc is the only identified component of the prion, an infectious agent that apparently does not contain nucleic acid. Models for how prions replicate require that PrPSc must somehow recruit PrPC and catalyze or stabilize a post-translational event that converts PrPC into PrPSc. Extensive characterization has suggested that this critical post-translational event is probably conformational and not a chemical change. The presence of a GPI anchor on CNTFR alpha is an unusual feature for a molecule that must transmit a signal to the inside of the cell. Recent data have indicated that CNTFR alpha must bind CNTF, then interact with two other "beta" receptor components to initiate signal transduction. Furthermore, we have shown that, unlike the vast majority of receptors, CNTFR alpha can function as a soluble molecule to promote CNTF action on cells that contain the two beta components, but do not themselves express CNTFR alpha. Intriguingly, we have also demonstrated that CNTFR alpha is present in cerebrospinal fluid and blood in vivo, and the release of CNTFR alpha from skeletal muscle is increased by denervation of the muscle. Whether the soluble form is released through GPI-anchor cleavage
remains to be determined.
release of GPI-bound proteins
Yoon, H.J., Park, S.W., Lee, H.B., Im, S.Y., Hooper, N.M. & Park, H.S. (2007) Arch. Pharm. Res. 30, 608-615. Release of renal dipeptidase from glycosylphosphatidylinositol anchor by insulin-triggered phospholipase C/intracellular Ca2+.
