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Endosome to Golgi Retrieval of the Vacuolar Protein Sorting Receptor, Vps10p, Requires the Function of the VPS29, VPS30, and VPS35 Gene Products

Seaman, Matthew N.J., Marcusson, Eric G., Cereghino, Joan Lin, Emr, Scott D.·1997·The Journal of Cell Biology
DOI 10.1083/jcb.137.1.79PMC PMC2139870
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Abstract

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.

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  • The retromer recycles specific cargos including CI-MPR, which is involved in delivery of proteolytic enzymes to lysosomes.

    “The retromer recycles specific cargos, such as Vps10/Sortilin protein family members14 or the cation-independent mannose 6-phosphate receptor (CI-MPR)15. The latter is involved in the delivery of proteolytic enzymes to lysosomes.”

    From Retromer stabilization results in neuroprotection in a model of Amyotrophic Lateral Sclerosis (2020) · cites this paper as [14]

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Metadata

Authors
Seaman, M. N. J., Marcusson, E. G., Cereghino, J. L., & Emr, S. D.
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
1997-04-07
Volume
137
Issue
1
Pages
79-92
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.137.1.79
PMC
PMC2139870
Cited by
378
References
0
Language
en

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