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Glycosylation directs targeting and activation of cystatin f from intracellular and extracellular sources.

ABSTRACT: 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.

SUBMITTER: Colbert JD

PROVIDER: S-EPMC2691902 | biostudies-other | 2009 Apr

REPOSITORIES: biostudies-other

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Glycosylation directs targeting and activation of cystatin f from intracellular and extracellular sources.

Colbert Jeff D JD Plechanovová Anna A Watts Colin C

Traffic (Copenhagen, Denmark) 20090124 4

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 ...[more]

PMID: 19192250

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Dataset Information

Glycosylation directs targeting and activation of cystatin f from intracellular and extracellular sources.

Publications

Glycosylation directs targeting and activation of cystatin f from intracellular and extracellular sources.

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