|
|
|
|
|
|
|
||
Division of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, School of
Medicine, La Jolla, California 92093-0668
Mutations in the S. cerevisiae VPS29 and
VPS30 genes lead to a selective protein sorting defect
in which the vacuolar protein carboxypeptidase Y
(CPY) is missorted and secreted from the cell, while
other soluble vacuolar hydrolases like proteinase A
(PrA) are delivered to the vacuole. This phenotype is
similar to that seen in cells with mutations in the previously characterized VPS10 and VPS35 genes. Vps10p is
a late Golgi transmembrane protein that acts as the
sorting receptor for soluble vacuolar hydrolases like
CPY and PrA, while Vps35p is a peripheral membrane
protein which cofractionates with membranes enriched
in Vps10p. The sequences of the VPS29, VPS30, and
VPS35 genes do not yet give any clues to the functions
of their products. Each is predicted to encode a hydrophilic protein with homologues in the human and
C. elegans genomes. Interestingly, mutations in the
VPS29, VPS30, or VPS35 genes change the subcellular
distribution of the Vps10 protein, resulting in a shift of
Vps10p from the Golgi to the vacuolar membrane. The
route that Vps10p takes to reach the vacuole in a vps35
mutant does not depend upon Sec1p mediated arrival
at the plasma membrane but does require the activity
of the pre-vacuolar endosomal t-SNARE, Pep12p. A
temperature conditional allele of the VPS35 gene was
generated and has been found to cause missorting/secretion of CPY and also Vps10p to mislocalize to a vacuolar membrane fraction at the nonpermissive temperature. Vps35p continues to cofractionate with Vps10p
in vps29 mutants, suggesting that Vps10p and Vps35p may directly interact. Together, the data indicate that
the VPS29, VPS30, and VPS35 gene products are required for the normal recycling of Vps10p from the prevacuolar endosome back to the Golgi where it can initiate additional rounds of vacuolar hydrolase sorting.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
