Routing Nanomolar Protein Cargoes to Lipid Raft-Mediated/Caveolar Endocytosis through a Ganglioside GM1-Specific Recognition Tag

Norbert Imre, Anasztázia Hetényi, Enikő Szabó, Brigitta Bodnár, Abel Szkalisity, Ilona Gróf, Alexandra Bocsik, Mária A. Deli, Peter Horvath, Ágnes Czibula, Éva Monostori, Tamás A. Martinek

Research output: Contribution to journalArticle

Abstract

There is a pressing need to develop ways to deliver therapeutic macromolecules to their intracellular targets. Certain viral and bacterial proteins are readily internalized in functional form through lipid raft-mediated/caveolar endocytosis, but mimicking this process with protein cargoes at therapeutically relevant concentrations is a great challenge. Targeting ganglioside GM1 in the caveolar pits triggers endocytosis. A pentapeptide sequence WYKYW is presented, which specifically captures the glycan moiety of GM1 (KD = 24 nm). The WYKYW-tag facilitates the GM1-dependent endocytosis of proteins in which the cargo-loaded caveosomes do not fuse with lysosomes. A structurally intact immunoglobulin G complex (580 kDa) is successfully delivered into live HeLa cells at extracellular concentrations ranging from 20 to 160 nm, and escape of the cargo proteins to the cytosol is observed. The short peptidic WYKYW-tag is an advantageous endocytosis routing sequence for lipid raft-mediated/caveolar cell delivery of therapeutic macromolecules, especially for cancer cells that overexpress GM1.

Original languageEnglish
Article number1902621
JournalAdvanced Science
Volume7
Issue number4
DOIs
Publication statusPublished - Feb 1 2020

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Keywords

  • cell delivery
  • endocytosis
  • glycan
  • immunoglobulin
  • peptides

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Imre, N., Hetényi, A., Szabó, E., Bodnár, B., Szkalisity, A., Gróf, I., Bocsik, A., Deli, M. A., Horvath, P., Czibula, Á., Monostori, É., & Martinek, T. A. (2020). Routing Nanomolar Protein Cargoes to Lipid Raft-Mediated/Caveolar Endocytosis through a Ganglioside GM1-Specific Recognition Tag. Advanced Science, 7(4), [1902621]. https://doi.org/10.1002/advs.201902621