Open AccessTwo proteins targeted to the same lytic granule compartment undergo very different posttranslational processing.
Author(s) -
Janis K. Burkhardt,
Susan Hester,
Yair Argon
Publication year - 1989
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.86.18.7128
Subject(s) - cytolysin , proteases , granzyme , biology , microbiology and biotechnology , biochemistry , serine , glycosylation , chemistry , perforin , phosphorylation , enzyme , cytotoxicity , virulence , gene , in vitro
The granules of natural killer (NK) cells contain cytolysin and serine proteases, proteins that are expressed specifically in cytolytic cells and are released in response to target binding. We have used immunofluorescence and immunoelectron microscopy to localize these proteins with respect to the various morphological compartments of granules in a rat NK cell line. Both cytolysin and the proteases are limited to the core regions of the dense core granules. While these proteins are targeted to the same compartment, they differ markedly in their posttranslational processing. Cytolysin bears N-linked oligosaccharides that are converted to the complex type, while the major trypsin-like protease, granzyme A, bears only high-mannose-type oligosaccharides. The glycans of granzyme A, but not those of cytolysin, are modified with phosphomannose moieties. These results suggest that one possible mechanism for packaging proteins into NK granules is the mannose 6-phosphate-dependent lysosomal targeting system. However, the absence of the mannose 6-phosphate modification from cytolysin suggests the existence of yet another targeting system.