Intracellular trafficking of lysosomal proteins and lysosomes

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

In the synthesis and trafficking of precursors of most lysosomal matrix proteins, the stages necessary for lysosomal delivery include the addition of phosphorylated mannose-rich oligosaccharides, binding of the modified proteins to receptors, their segregation from the secretory pathways and delivery to the endosomal pathway. Targeting of both internally synthesized and externally provided enzymes (as in enzyme replacement therapy) to endosomes is executed by a complex machinery of membrane and cytosolic proteins. Recently, the homotypic fusion and vacuolar protein sorting (HOPS) complex has been identified in lysosomes from human cells. This complex is likely to play an important role in the exchange of enzymes between endosomal and lysosomal compartments. The present review describes the interactions and functions of proteins that participate in delivering lysosomal proteins to different lysosomal compartments. In summary, lysosomal trafficking depends on the recognition of many structural signals. It delivers soluble and membrane proteins, and can be exploited for therapeutic substitution of missing enzymes.

Details

Original languageEnglish
Pages (from-to)S18-S33
JournalInternational journal of clinical pharmacology and therapeutics
Volume47
Issue numberSUPPL. 1
Publication statusPublished - 2009
Peer-reviewedYes

External IDs

PubMed 20040308

Keywords

ASJC Scopus subject areas

Keywords

  • Adaptors, Enzyme replacement therapy, Exocytosis, HOPS complex, Lysosomal trafficking, Receptors, Storage diseases, Targeting, Trans-Golgi network