Glycosylation Directs Targeting and Activation of Cystatin F from Intracellular and Extracellular Sources
| Autor: | Anna Plechanovová, Jeff D. Colbert, Colin Watts |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Glycosylation
Endosome cathepsin C Protein Conformation Molecular Sequence Data Oligosaccharides Mannose 6-phosphate Endosomes Biology urologic and male genital diseases Biochemistry mannose 6-phosphate Cathepsin C Cell Line 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Structural Biology Genetics Biomarkers Tumor Animals Humans Amino Acid Sequence Molecular Biology cystatin Secretory pathway reproductive and urinary physiology 030304 developmental biology 0303 health sciences Mannosephosphates Cell Biology Original Articles Cysteine protease Cystatins female genital diseases and pregnancy complications Cell biology chemistry 030220 oncology & carcinogenesis Cystatin A Mutagenesis Site-Directed Cystatin Asparagine endocytosis/internalization Dimerization |
| Zdroj: | Traffic (Copenhagen, Denmark) |
| ISSN: | 1600-0854 1398-9219 |
| Popis: | Cystatin F is a cysteine protease inhibitor that is selectively expressed in immune cells and unlike other cystatin family members is targeted to a significant extent to intracellular compartments. Initially made as an inactive glycosylated disulfide-linked dimer, cystatin F is converted to an active monomer by proteolytic cleavage following transport to the endosomal/lysosomal system. This active form of cystatin F targets cathepsin C/DPPI and probably other cathepsins in immune cells. We show that efficient targeting of cystatin F to the endocytic pathway is dependent not on its unique dimeric conformation but rather on its oligosaccharide chains. We demonstrate the unusual addition of N-linked sugars to an Asn-X-Cys motif in cystatin F and provide evidence that the mannose 6-phosphate sorting machinery is used to divert cystatin F from the secretory pathway and to mediate its uptake from extracellular pools. These studies identify a function for the oligosaccharides on cystatin F and raise the possibility that cystatin F might regulate proteases in trans by secretion in an inactive form by one cell and subsequent internalization and activation by another cell. |
| Databáze: | OpenAIRE |
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