A novel mechanism for protein delivery: granzyme B undergoes electrostatic exchange from serglycin to target cells

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Srikumar M Raja
  • Sunil S Metkar
  • Stefan Honing
  • Baikun Wang
  • William A Russin
  • Nina H Pipalia
  • Cheikh Menaa
  • Mattias Belting
  • Xuefang Cao
  • Ralf Dressel
  • Christopher J Froelich
External organisations
  • Scripps Research Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)20752-20761
JournalJournal of Biological Chemistry
Volume280
Issue number21
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes