RRC ID 2195
Author Ma Y, Kuno T, Kita A, Nabata T, Uno S, Sugiura R.
Title Genetic evidence for phospholipid-mediated regulation of the Rab GDP-dissociation inhibitor in fission yeast.
Journal Genetics
Abstract We have previously identified mutant alleles of genes encoding two Rab proteins, Ypt3 and Ryh1, through a genetic screen using the immunosuppressant drug FK506 in fission yeast. In the same screen, we isolated gdi1-i11, a mutant allele of the essential gdi1+ gene encoding Rab GDP-dissociation inhibitor. In gdi1-i11, a conserved Gly267 was substituted by Asp. The Gdi1G267D protein failed to extract Rabs from membrane and Rabs were depleted from the cytosolic fraction in the gdi1-i11 mutant cells. Consistently, the Gdi1G267D protein was found mostly in the membrane fraction, whereas wild-type Gdi1 was found in both the cytosolic and the membrane fraction. Notably, overexpression of spo20+, encoding a phosphatidylcholine/phosphatidylinositol transfer protein, rescued gdi1-i11 mutation, but not ypt3-i5 or ryh1-i6. The gdi1-i11 and spo20-KC104 mutations are synthetically lethal, and the wild-type Gdi1 failed to extract Rabs from the membrane in the spo20-KC104 mutant. The phosphatidylinositol-transfer activity of Spo20 is dispensable for the suppression of the gdi1-i11 mutation, suggesting that the phosphatidylcholine-transfer activity is important for the suppression. Furthermore, knockout of the pct1+ gene encoding a choline phosphate cytidyltransferase rescued the gdi1-i11 mutation. Together, our findings suggest that Spo20 modulates Gdi1 function via regulation of phospholipid metabolism of the membranes.
Volume 174(3)
Pages 1259-71
Published 2006-11-1
DOI 10.1534/genetics.106.064709
PII genetics.106.064709
PMID 16980382
PMC PMC1667090
MeSH Alleles Amino Acid Sequence Amino Acid Substitution Asparagine / metabolism Gene Deletion Genes, Fungal Genetic Complementation Test Golgi Apparatus / ultrastructure Guanine Nucleotide Dissociation Inhibitors / genetics Guanine Nucleotide Dissociation Inhibitors / metabolism* Molecular Sequence Data Phospholipids / metabolism* Schizosaccharomyces / genetics* Schizosaccharomyces / physiology* Schizosaccharomyces / ultrastructure Sequence Homology, Amino Acid rab GTP-Binding Proteins / genetics rab GTP-Binding Proteins / metabolism*
IF 4.015
Times Cited 9
Yeast HM123