The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Internalization of HIV-1 Tat Requires Cell Surface Heparan Sulfate Proteoglycans
Open accessAbstract
Tat, the transactivator protein of human immunodeficiency virus-1, has the unusual capacity of being internalized by cells when present in the extracellular milieu. This property can be exploited for the cellular delivery of heterologous proteins fused to Tat both in cell culture and in living animals. Here we provide genetic and biochemical evidence that cell membrane heparan sulfate (HS) proteoglycans act as receptors for extracellular Tat uptake. Cells genetically defective in the biosynthesis of fully sulfated HS are selectively impaired in the internalization of recombinant Tat fused to the green fluorescent protein, as evaluated by both flow cytometry and functional assays. In wild type cells, Tat uptake is competitively inhibited by soluble heparin and by treatment with glycosaminoglycan lyases specifically degrading HS chains. Cell surface HS proteoglycans also mediate physiological internalization of Tat green fluorescent protein released from neighboring producing cells. In contrast to extracellular Tat uptake, both wild type cells and cells genetically impaired in proteoglycan synthesis are equally proficient in the extracellular release of Tat, thus indicating that proteoglycans are not required for this process. The ubiquitous distribution of HS proteoglycans is consistent with the efficient intracellular delivery of heterologous proteins fused with Tat to different mammalian cell types.
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Citations
Cites
Tat trans-activates the human immunodeficiency virus through a nascent RNA target
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Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds
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Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins
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The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line
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“These enzymes play important roles in the generation of heparan sulfate, which is known to be important for entry of viruses such as HI”
CNS Delivery Via Adsorptive Transcytosis
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Metadata
- Authors
- Tyagi, M., Rusnati, M., Presta, M., & Giacca, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 276
- Issue
- 5
- Pages
- 3254-3261
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2055296721
- Cited by
- 719
- References
- 1
- FWCI
- 13.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
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