High impact information on VPS1

• Analysis of the CHS polypeptide demonstrates that its modular architecture is similar to the yeast vacuolar sorting protein, VPS15 [1].
• This protein, the VPS1 product, is essential for vacuolar protein sorting, normal organization of intracellular membranes, and growth at high temperature, implying that Mx-like proteins are engaged in fundamental cellular processes in eukaryotes [2].
• This protein is identical to VPS1, a gene involved in vacuolar protein sorting in yeast which has significant sequence homology (45% overall, 66% over 300 amino acids) to the microtubule bundling-protein, dynamin [3].
• Here, we have found that disruptions in the genes encoding a dynamin-related protein (VPS1) or clathrin heavy chain (CHC1) abolish HDSV production, yielding LDSVs that contain all secreted cargos [4].
• Golgi and vacuolar membrane proteins reach the vacuole in vps1 mutant yeast cells via the plasma membrane [5].

Biological context of VPS1

• One such suppressor, MVP1, that exhibits genetic interaction with VPS1 and is itself required for vacuolar protein sorting has been isolated [6].
• This suggests that deletion of DNM1 reinforces the vps1 peroxisome phenotype [7].
• Tightly centromere-linked gene (SPO15) essential for meiosis in the yeast Saccharomyces cerevisiae [8].
• Furthermore, a defect in endocytic delivery to the vacuole was revealed in vps8 (and vps36) but not vps1 by endocytosis of the bulk membrane marker FM 4-64 [9].
• DNA sequence analysis of the mutant vps1 allele (vps1d-293) revealed a single point mutation, resulting in an amino acid exchange at position 293 from Ala to Asp [10].

Anatomical context of VPS1

• Previous data from glucose-grown VPS1 and DNM1 null mutants suggested that Vps1p, but not Dnm1p, plays a role in regulating peroxisome abundance [7].
• The VPS1 gene of Saccharomyces cerevisiae encodes an 80-kDa GTPase that associates with Golgi membranes and is required for the sorting of proteins to the yeast vacuole [6].
• Vacuolar protein precursors are secreted by lam1 mutants, revealing another sorting defect in the Golgi complex [11].
• The association can also be observed between natively expressed proteins in a panel of hematopoietic and nonhematopoietic cell lines, where a second subunit of the ESCRT complex, vacuolar sorting protein 28 (Vps28), was also found to interact with Bcr [12].

Associations of VPS1 with chemical compounds

• A significant fraction of oleate-induced vps1 cells still contained two or more peroxisomes [7].
• When VPS1 was treated with hydroxylamine, half of all mutations isolated were found to be dominant negative with respect to vacuolar protein sorting [13].
• Organelle fractionation by sucrose density gradient centrifugation shows that Kex2p is not retained in the Golgi complex of lam1 cells [11].
• Similar to Vps1, VpsA contains a highly conserved tripartite GTPase domain but lacks the pleckstrin homology domain and proline-rich region [14].

Physical interactions of VPS1

• The Saccharomyces cerevisiae MVP1 gene interacts with VPS1 and is required for vacuolar protein sorting [6].

Regulatory relationships of VPS1

• Overproduction of Mvp1p will suppress several dominant alleles of VPS1, and suppression is dependent on the presence of wild-type Vps1p [6].

Other interactions of VPS1

• Striking genetic interactions were observed by combining temperature-sensitive alleles of CHC1 and VPS1, supporting the model that Vps1p is involved in clathrin-mediated vesicle formation at the TGN [15].
• Quantitative analysis revealed a greater reduction in peroxisome number in oleate-induced vps1 cells relative to dnm1 or fis1 cells [7].
• These data support a model in which mutant Pma1 is diverted from the Golgi to the surface in vps1 cells [9].
• In lam1 cells, Kex2p is not mislocalized to the cell surface but is abnormally unstable [11].
• As was observed with the late Golgi protein Kex2p, Vps10p is unstable in a vps1 mutant [16].

Analytical, diagnostic and therapeutic context of VPS1

• In addition, sequence analysis revealed three recently functionally characterized genes (MET14, VPS/SPO15, PAP1), which could be joined to the earlier published CEN11 region [17].

References