High impact information on GPI1

• Disruption of GPI1 yields viable haploid cells that are temperature-sensitive for growth, for [3H]inositol incorporation into protein, and for GPI anchor-dependent processing of the Gas1/Ggp1 protein and that lack in vitro N-acetylglucosaminylphosphatidylinositol synthetic activity [1].
• We report the isolation of two more conditionally lethal mutants, gpi2 and gpi3, which, like gpi1, have a temperature-sensitive defect in the incorporation of [3H]inositol into protein and which lack in vitro GlcNAc-phosphatidylinositol synthetic activity [2].
• Using random spore analysis, we were able to show that the mammalian GPI1 homologues can rescue haploids harbouring the lethal gpi1+::his7+ allele [3].
• In Sacch. cerevisiae, where GPI1 disruption results in a temperature-sensitive phenotype and abolishes in vitro GlcNAc-PI synthesis, restoration of growth could be demonstrated in a temperature-dependent manner [3].
• In a yeast gpi1 mutant, a green-fluorescent-protein-tagged Kre1p derivative is secreted into the medium, indicating an at least transient GPI-anchoring stage of Kre1p during its processing within the yeast secretory pathway [4].

Biological context of GPI1

• Like the other GPI1 proteins, the predictive software revealed the absence of targeting signals such as organelle transit peptides, DNA binding sites, or N-terminal secretory signals [5].
• The potential tyrosine phosphorylation site seems to occur in all other known Gpi1 proteins [5].
• Analysis showed that P. falciparum Gpi1p is somewhat more similar to the yeast proteins than human Gpi1p, showing 26 and 20% amino acid sequence identity with the Saccharomyces cerevisiae and Homo sapiens proteins, respectively [5].
• We have isolated plasmids that complement the gpi1 mutation from S. cerevisiae genomic DNA-and fission yeast cDNA libraries [6].

Other interactions of GPI1

• This reaction is carried out by a protein complex, three of whose subunits in humans, hGpi1p, Pig-Cp and Pig-Ap, have sequence and functional homologues in the Saccharomyces cerevisiae Gpi1, Gpi2 and Gpi3 proteins, respectively [7].

Analytical, diagnostic and therapeutic context of GPI1

• Multiple sequence alignment demonstrates also that the C-terminal half GPI1 proteins is much better conserved than the N-terminal half [5].

References