Disease relevance of GPI8

• GPI8 from Trypanosoma brucei was cloned and expressed in Escherichia coli [1].

High impact information on GPI8

• These findings suggest that Gab1p is a subunit of the GPI transamidase with distinct relationships to other subunits in the same complex [2].
• The mammalian GPI transamidase is a complex of at least four subunits, GPI8, GAA1, PIG-S, and PIG-T [3].
• We have characterized T. brucei GPI8, the gene encoding the catalytic subunit of the GPI:protein transamidase complex that adds preformed GPI anchors onto nascent polypeptides [4].
• These data show that GPI-anchored proteins are essential for the viability of bloodstream form trypanosomes even in the absence of immune challenge and imply that GPI8 is important for proper cell cycle progression [4].
• Applying specific inducible GPI8 RNAi with bloodstream form parasites resulted in accumulation of unanchored variant surface glycoprotein and cell death with a defined multinuclear, multikinetoplast, and multiflagellar phenotype indicative of a block in cytokinesis [4].

Biological context of GPI8

• This review summarizes the current aggregate of biochemical, gene-disruption and active site mutagenesis studies, which provide evidence that GPI8 is responsible for the protein-GPI anchoring reaction [5].

Anatomical context of GPI8

• Antibodies raised against L. mexicana GPI8 detected a protein of approx. 38 kDa in an immunoblot of the high-pH extract of trypanosome membranes [6].
• Soluble GPI8 restores glycosylphosphatidylinositol anchoring in a trypanosome cell-free system depleted of lumenal endoplasmic reticulum proteins [6].
• We have cloned the L. mexicana GPI8 gene that encodes the catalytic component of the GPI:protein transamidase complex that adds GPI anchors to nascent cell surface proteins in the endoplasmic reticulum [7].
• Immune fluorescence microscopy revealed co-localisation with the GPI:protein transamidase component, GPI8, a distribution indicative of ribosome association with the rough endoplasmic reticulum [8].

Associations of GPI8 with chemical compounds

• Activity could also be restored by reconstituting the inactivated membranes with Escherichia coli-expressed, polyhistidine-tagged Leishmania mexicana GPI8 (GPI8-His; L. mexicana GPI8 is a soluble homologue of yeast and mammalian Gpi8p) [6].
• GPI8 functions dually to perform the proteolytic cleavage of the C-terminal signal sequence of the precursor protein, followed by the formation of an amide bond between the protein and the ethanolamine phosphate of the GPI [5].

Other interactions of GPI8

• Moreover, Gpi8p becomes unstable when any one of the other subunits is depleted, whereas Gpi17p is slightly affected only by the depletion of Gaa1p [9].
• Overexpression of Gpi8p cannot compensate for the lack of Gpi16p [10].

References