High impact information on PEP7

• Our data establish a molecular link between Vps34 PI(3)K and several FYVE domain-containing proteins (Vac1p, Vps27p) required for vacuolar/lysosomal protein trafficking [1].
• In semi-intact cells, formation of tubulovesicular structures requires ATP and the proteins encoded by VAC1 and VAC2, two genes which are required for vacuole inheritance in vivo [2].
• High copy PEP7/VAC1 suppresses vacuolar morphology defects of vps33 mutants [3].
• We propose that activated-Vps21p interacts with its effector, Vac1p, which interacts with Vps45p to regulate the Golgi to endosome SNARE complex [4].
• We have constructed an activated allele of VPS21, a yeast Rab protein involved in vacuolar protein sorting, and demonstrated an allele-specific interaction between Vps21p and Vac1p [4].

Biological context of PEP7

• Temperature-sensitive-for-function (tsf) and dominant negative mutations in PEP12, encoding a putative SNARE vesicle receptor on the endosome, and tsf mutations in VAC1, a gene implicated in vacuole inheritance and vacuolar protein sorting, were constructed and used to demonstrate that Pep12p and Vac1p are components of the VPS pathway [5].
• The sequence of Vac1p contains two putative zinc-binding RING motifs, a zinc finger motif, and a coiled-coil motif [5].
• Vac1p FYVE finger mutant missorting phenotypes were suppressed by a defective allele of VPS34 [4].
• In addition, the loss of Vac1p affected several virulence factors of C. albicans [6].

Anatomical context of PEP7

• The PEP7 gene from Saccharomyces cerevisiae encodes a 59-kD hydrophilic polypeptide that is required for transport of soluble vacuolar hydrolase precursors from the TGN to the endosome [7].
• Vac1p was found to be tightly associated with membranes as a monomer and in a large SDS-resistant complex [5].
• Genetic interactions between a pep7 mutation and the PEP12 and VPS45 genes: evidence for a novel SNARE component in transport between the Saccharomyces cerevisiae Golgi complex and endosome [7].
• Whereas pep7 mutants demonstrate no defects in endocytic uptake at the plasma membrane, the mutants demonstrate defects in transport of receptor-mediated macromolecules through the endocytic pathway [8].
• The vesicle transport protein Vac1p is required for virulence of Candida albicans [6].

Associations of PEP7 with chemical compounds

• Vac1p contains a zinc-binding FYVE finger that may bind phosphatidylinositol 3-phosphate [PtdIns(3)P] [4].
• Mutations that change highly conserved cysteine residues in this motif lead to a loss of Pep7p function [8].
• Vac1p also contributes to resistance to metal ions, as the null mutant strain was hypersensitive to Cu(2+), Zn(2+) and Ni(2+) [6].

Physical interactions of PEP7

• The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting [4].
• Moreover, the Class D protein Vac1 was found to physically bind to the Class C Vps complex through a direct association with Vps11 [9].

Other interactions of PEP7

• The functions of Pep12p, Vps45p, and Vps21p indicate that key aspects of Golgi-to-endosome trafficking are similar to other vesicle-mediated transport steps, although the role of Vac1p suggests that there are also novel components of the VPS pathway [5].
• These fingers also show limited conservation with S. cerevisiae VAC1, Vps11, and Vps18p proteins implicated in vacuolar transport [10].
• We suggest that the ability of the VPS3, VPS8 and PEP7 genes to rescue lethal effects of oxidative damage resulted from the overexpression of these genes [11].
• Kinetic studies demonstrate that Pep7p function is required for the transport of the Golgi-precursors of the soluble hydrolases carboxypeptidase Y, proteinase A, and proteinase B to the endosome [8].

References