High impact information on VPS8

• Additional alleles in each of the eight previously identified vpt complementation groups (vpt1 through vpt8) were also obtained [1].
• At the endosome, Vps33p and other class C members exist as a complex with Vps8p, a protein previously known to act in transport between the late Golgi and the endosome [2].
• In both vps1 and vps8 cells, newly synthesized mutant Pma1 appears in small punctate structures before arrival at the cell surface [3].
• 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 [3].
• In this study, we have analyzed trafficking in the endosomal system by monitoring the movement of Pma1-7 in vps36, vps1, and vps8 mutants [3].

Biological context of VPS8

• This sorting is not blocked by a temperature-sensitive mutation in SEC12, which inhibits ER to Golgi transport, a null mutation in VPS8, which inhibits Golgi to PVC transport, or temperature-sensitive and null mutations in END4, which inhibit endocytosis from the plasma membrane [4].
• To better understand the process of protein sorting to the yeast vacuole, the VPS8 gene was identified and characterized [5].
• Moreover, in vps8 cells, there is defective down-regulation from the cell surface of the mating receptor Ste3, consistent with persistent receptor recycling from an endosomal compartment to the plasma membrane [3].

Anatomical context of VPS8

• PEP5 interacts genetically with VPS8, implicating Pep5p in the earlier Golgi to endosome step and/or in recycling from the endosome to the Golgi [6].
• These observations indicate that ALP is sorted to the vacuole in a Vps8p-independent manner, possibly via an alternative vesicle carrier [7].
• In vps21 null mutant cells, Vps8p is found in the cytosol [7].
• This genetic interaction was unexpected, since Pep5p was thought to interact more directly with the vacuole, and Vps8p is thought to play a role in transport between the Golgi complex and the prevacuolar compartment [8].
• Based on our findings, we propose that Vps8p is part of a protein complex that associates with Golgi and post-Golgi membranes and functions in the retrieval of Golgi membrane proteins from the prevacuolar compartment [5].

Associations of VPS8 with chemical compounds

• Vps8p contains a C-terminal cysteine-rich region that conforms to the H2 variant of the RING finger Zn2+ binding motif [7].

Other interactions of VPS8

• This approach identified the VPS3, VPS8 and PEP7 genes that function in vesicular trafficking between the endosome and the yeast vacuole via the carboxypeptidase Y (CpY) pathway [9].
• 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 [9].
• The data are consistent with Pep5p functioning both at the site of Vps8p function and more closely proximal to the vacuole [8].

References