A Novel Mechanism for Protein Delivery

The molecular interaction of secreted granzyme B-serglycin complexes with target cells remains undefined. Targets exposed to double-labeled granzyme B-serglycin complexes show solely the uptake of granzyme B. An in vitro model demonstrates the exchange of the granzyme from serglycin to immobilized,...

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Published inThe Journal of biological chemistry Vol. 280; no. 21; pp. 20752 - 20761
Main Authors Raja, Srikumar M., Metkar, Sunil S., Höning, Stefan, Wang, Baikun, Russin, William A., Pipalia, Nina H., Menaa, Cheikh, Belting, Mattias, Cao, Xuefang, Dressel, Ralf, Froelich, Christopher J.
Format Journal Article
LanguageEnglish
Published Elsevier Inc 27.05.2005
American Society for Biochemistry and Molecular Biology
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Summary:The molecular interaction of secreted granzyme B-serglycin complexes with target cells remains undefined. Targets exposed to double-labeled granzyme B-serglycin complexes show solely the uptake of granzyme B. An in vitro model demonstrates the exchange of the granzyme from serglycin to immobilized, sulfated glycosaminoglycans. Using a combination of cell binding and internalization assays, granzyme B was found to exchange to sulfated glycosaminoglycans and, depending on the cell type, to higher affinity sites. Apoptosis induced by purified granzyme B and cytotoxic T-cells was diminished in targets with reduced cell surface glycosaminoglycan content. A mechanism of delivery is proposed entailing electrostatic transfer of granzyme B from serglycin to cell surface proteins.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M501181200