Proteasome inhibitors block a late step in lysosomal transport of selected membrane but not soluble proteins

P. Van Kerkhof, C. M. Alves dos Santos, M. Sachse, J. Klumperman, G. Bu, G. J. Strous

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

The ubiquitin-proteasome pathway acts as a regulator of the endocytosis of selected membrane proteins. Recent evidence suggests that it may also function in the intracellular trafficking of membrane proteins. In this study, several models were used to address the role of the ubiquitinproteasome pathway in sorting of internalized proteins to the lysosome. We found that lysosomal degradation of ligands, which remain bound to their receptors within the endocytic pathway, is blocked in the presence of specific proteasome inhibitors. In contrast, a ligand that dissociates from its receptor upon endosome acidification is degraded under the same conditions. Quantitative electron microscopy showed that neither the uptake nor the overall distribution of the endocytic marker bovine serum albumin-gold is substantially altered in the presence of a proteasome inhibitor. The data suggest that the ubiquitin-proteasome pathway is involved in an endosomal sorting step of selected membrane proteins to lysosomes, thereby providing a mechanism for regulated degradation.

Original languageEnglish (US)
Pages (from-to)2556-2566
Number of pages11
JournalMolecular biology of the cell
Volume12
Issue number8
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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