Glycosylphoshatidylinositol (GPI) anchors are remodeled during their transport to the cell surface. Newly synthesized proteins are transferred to a GPI anchor, consisting of diacylglycerol with conventional C16 and C18 fatty acids, whereas the lipid moiety in mature GPI-anchored proteins is exchanged to either diacylglycerol containing a C26:0 fatty acid in the sn-2 position or ceramide in Saccharomyces cerevisiae. Here, we report on PER1, a gene encoding a protein that is required for the GPI remodeling pathway. We found that GPI-anchored proteins could not associate with the detergent-resistant membranes in per1Delta cells. In addition, the mutant cells had a defect in the lipid remodeling from normal phosphatidylinositol (PI) to a C26 fatty acid-containing PI in the GPI anchor. In vitro analysis showed that PER1 is required for the production of lyso-GPI, suggesting that Per1p possesses or regulates the GPI-phospholipase A2 activity. We also found that human PERLD1 is a functional homologue of PER1. Our results demonstrate for the first time that PER1 encodes an evolutionary conserved component of the GPI anchor remodeling pathway, highlighting the close connection between the lipid remodeling of GPI and raft association of GPI-anchored proteins.
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| Gene/Complex | Qualifier | Gene Ontology Term | Annotation Extension | Evidence | Source | Assigned On |
|---|---|---|---|---|---|---|
| PER1 | located in | endoplasmic reticulum | IDA | SGD | 2013-08-07 | |
| PER1 | involved in | GPI anchor biosynthetic process | IMP | SGD | 2013-08-07 |
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| Gene | Phenotype | Experiment Type | Mutant Information | Strain Background | Chemical | Details |
|---|---|---|---|---|---|---|
| PER1 | heat sensitivity: increased | classical genetics | null Allele: per1-Δ | S288C | Temperature: elevated temperature, 37 °C | |
| PER1 | heat sensitivity: increased | classical genetics | reduction of function Allele: per1-H177A | S288C | Temperature: elevated temperature, 37 °C | |
| PER1 | heat sensitivity: increased | classical genetics | reduction of function Allele: per1-H326A | S288C | Temperature: elevated temperature, 37 °C | |
| PER1 | resistance to chemicals: decreased | classical genetics | null Allele: per1-Δ | S288C | Calcofluor White | |
| PER1 | resistance to chemicals: decreased | classical genetics | reduction of function Allele: per1-H177A | S288C | Calcofluor White | |
| PER1 | resistance to chemicals: decreased | classical genetics | reduction of function Allele: per1-H326A | S288C | Calcofluor White |