Glycosylphosphatidyl-inositol anchor

Glycosylphosphatidyl inositol anchors constitute a class of glycolipids that link proteins and glycoproteins via their C-terminus to eukaryotic cell membranes. The first structure of a GPI anchor, that of Trypanosoma brucei, was published by Ferguson et al. [262]. Since then quite a few examples of GPI anchors were described, allowing the definition of the core structure depicted inO Scheme 37 [263]. 

Suzuki, K., Watanabe, T., Sakurai, S., Ohtake, K., Kinoshita, T., Araki, A., Fujita, T., Takei, H., Takeda, Y., Sato, Y., Yamashita, T., Araki, Y., and Sendo, F., 1999. A novel glycosylphosphatidyl inositol-anchored protein on human leukocytes a possible role for regulation of neutrophil adherence and migration. The Journal of Immunology. 162 4277-4284. 

SOME PROTEINS ARE ANCHORED TO THE PLASMA MEMBRANE BY GLYCOSYLPHOSPHATIDYL-INOSITOL STRUCTURES... 

About 10-20% of all transmembrane proteins that are targeted to the ER and subsequently enter the secretory pathway are subject to post-translational modification with glycosylphosphatidyl-inositol (GPI). Proteins bearing the GPI anchor are involved in signal transduction, immune response, cancer cell invasion, and metastasis and the pathobiology of trypanosomal parasites. The structure of the GPI anchor has been analyzed for mammals, protozoa, and yeast. The general structure of the glycolipid structure is shown in Scheme 4. 

Rai, S.K. et al., Candidate tumor suppressor HYAL2 is glycosylphosphatidyl inositol (GPI)-anchored cell-surface receptor for jaagsiekte sheep retrovirus, the envelope protein of which mediates oncogenic transformation, Proc. Natl Acad. Sci. USA, 98, 4443, 2001. 

Recently, CD52 glycopeptide 17 with an acid-labile fucosidic linkage was also prepared by this new method (Scheme 4). CD52 is a glycosylphosphatidyl-inositol (GPI)-anchored glycopeptide that plays an important role in the human immune system (29,30) and human reproduction process (31-33). 

All aminopeptidases identified so far contain a glycosylphosphatidyl inositol (GPI) moiety through which they anchor to membranes [123,124,143,144]. These GPI-anchored proteins may play an essential role in targeting Cry toxins to lipid raft membrane microdomains and leading to toxin aggregation and pore fimnation [145]. Removal of the GPI-anchor with bacterial or endogenous phospholipase C converts flie membrane-... 

Fig. 3. Model of the life cycle of prions. PrP is synthesized in the rough endoplas-matic reticulum (ER), and after passing through the secretory pathway including the Golgi and secretory vesicles, reaches the surface of a PrP infectable cell where it is anchored via a glycosylphosphatidyl inositol (GPI) moiety. Endocytosis of PrP and possibly PrP via clathrin coated vesicles could be mediated by the 37 kDa laminin receptor precursor (LRP). The uptake of the infectious agent could also be LRP independent. The conversion of the internalized PrP to PrP is thought to take place in the endo-somes, lysosomes, or endolysosomes. Molecular chaperones could be involved in this conversion process. PrP replication and aggregation can occur in neuronal cells of the brain but also in the cells constituting the lymphoreticular system. Alternatively, endocytosis and conversion of PrP into PrP could happen in caveolae-like domains (CLDs).

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