Yeast Vps55p, a functional homolog of human obesity receptor gene-related protein, is involved in late endosome to vacuole trafficking.
The Saccharomyces cerevisiae VPS55 (YJR044c) gene encodes a small protein of 140 amino acids with four potential transmembrane domains. VPS55 belongs to a family of genes of unknown function, including the human gene encoding the obesity receptor gene-related protein (OB-RGRP). Yeast cells with a disrupted VPS55 present normal vacuolar morphology, but exhibit an abnormal secretion of the Golgi form of the soluble vacuolar carboxypeptidase Y. However, trafficking of the membrane-bound vacuolar alkaline phosphatase remains normal. The endocytosis of uracil permease, used as an endocytic marker, is normal in vps55Delta cells, but its degradation is delayed and this marker transiently accumulates in late endosomal compartments. We also found that Vps55p is mainly localized in the late endosomes. Collectively, these results indicate that Vps55p is involved in late endosome to vacuole trafficking. Finally, we show that human OB-RGRP displays the same distribution as Vps55p and corrects the phenotypic defects of the vps55Delta strain. Therefore, the function of Vps55p has been conserved throughout evolution. This study highlights the importance of the multispanning Vps55p and OB-RGRP in membrane trafficking to the vacuole/lysosome of eukaryotic cells.
Belgareh-Touzé
Naïma
N
Jacques Monod Institute, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7592, Universities Paris VI and VII, Paris Cedex 05, France.
Avaro
Sandrine
S
Rouillé
Yves
Y
Hoflack
Bernard
B
Haguenauer-Tsapis
Rosine
R
D002268:Carboxypeptidases / Q000096:biosynthesis / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D043402:Cathepsin A; D011992:Endosomes / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007546:Isoquinolines / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009154:Mutation; D033704:Nucleotide Transport Proteins / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D014498:Uracil / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; C035528:FUR4 protein, S cerevisiae; D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D047908:Intracellular Signaling Peptides and Proteins; D007546:Isoquinolines; C107590:LEPROT protein, human; D008565:Membrane Proteins; D033704:Nucleotide Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C066755:Sec7 guanine nucleotide exchange factors; D033921:Vesicular Transport Proteins; C468123:Vps55 protein, S cerevisiae; D014498:Uracil; C017475:lucifer yellow; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A