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journal article·2020-02Open access

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

Advanced Science· Volume 7· Issue 4
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Source abstract

Abstract

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.
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Research context

PolymersNanomaterials

OpenAlex topics: Glycosylation and Glycoproteins Research · Bacteriophages and microbial interactions · Monoclonal and Polyclonal Antibodies Research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Medical Chemistry University of Szeged Dóm tér 8 Szeged HU‐6720 Hungary

Institute of Genetics Biological Research Center (BRC) Temesvári krt. 62 Szeged HU‐6726 Hungary

MTA‐SZTE Biomimetic Systems Research Group University of Szeged Dóm tér 8 Szeged HU‐6720 Hungary

Synthetic and Systems Biology Unit Biological Research Center (BRC) Temesvári krt. 62 Szeged HU‐6726 Hungary

Institute of Biophysics Biological Research Center (BRC) Temesvári krt. 62 Szeged HU‐6726 Hungary

Doctoral School of Biology University of Szeged Dugonics tér 13 Szeged HU‐6720 Hungary

Department of Cell Biology and Molecular Medicine University of Szeged Somogyi u. 4 Szeged HU‐6720 Hungary

Institute for Molecular Medicine Finland University of Helsinki Tukholmankatu 8 Helsinki FI‐00014 Finland

Funding

National Research, Development and Innovation Office of Hungary · Hungarian Ministry of Innovation and Technology · Hungarian National Brain Research Program · Hungarian Academy of Sciences LENDULET-Foldamer · Hungarian Academy of Sciences LENDULET-Biomag

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