Involvement of specific COPI subunits in protein sorting from the late endosome to the vacuole in yeast.
Although COPI function on the early secretory pathway in eukaryotes is well established, earlier studies also proposed a nonconventional role for this coat complex in endocytosis in mammalian cells. Here we present results that suggest an involvement for specific COPI subunits in the late steps of endosomal protein sorting in Saccharomyces cerevisiae. First, we found that carboxypeptidase Y (CPY) was partially missorted to the cell surface in certain mutants of the COPIB subcomplex (COPIb; Sec27, Sec28, and possibly Sec33), which indicates an impairment in endosomal transport. Second, integral membrane proteins destined for the vacuolar lumen (i.e., carboxypeptidase S [CPS1]; Fur4, Ste2, and Ste3) accumulated at an aberrant late endosomal compartment in these mutants. The observed phenotypes for COPIb mutants resemble those of class E vacuolar protein sorting (vps) mutants that are impaired in multivesicular body (MVB) protein sorting and biogenesis. Third, we observed physical interactions and colocalization between COPIb subunits and an MVB-associated protein, Vps27. Together, our findings suggest that certain COPI subunits could have a direct role in vacuolar protein sorting to the MVB compartment.
Gabriely
Galina
G
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Kama
Rachel
R
Gerst
Jeffrey E
JE
D043402:Cathepsin A / Q000378:metabolism; D020755:Coat Protein Complex I / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism*; D006867:Hydrolases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014617:Vacuoles / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000378:metabolism
D020755:Coat Protein Complex I; D056827:Endosomal Sorting Complexes Required for Transport; D008565:Membrane Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C119627:VPS27 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D006867:Hydrolases; D043402:Cathepsin A