NEW EMBO MEMBERS' REVIEW: Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives

Sandvig, Kirsten; Deurs, Bo van

doi:10.1093/emboj/19.22.5943

Cited by 238 publications

(180 citation statements)

References 99 publications

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“…56 and 57). These toxins, such as ricin and Shiga toxin, consist of a membrane-binding subunit (B subunit) and an enzymatically active moiety (A subunit) (56). Interestingly a sequence comparison with the Tat and Antp peptides revealed a highly conserved arginine-rich motif of 8 -10 amino acids in the A subunits of several toxins, which are reported to be transported by means of retrograde transport (Table II).…”

Section: Impact Of Golgi-disrupting Agents On the Uptake And Distribumentioning

confidence: 99%

A Stepwise Dissection of the Intracellular Fate of Cationic Cell-penetrating Peptides

Fischer

Köhler

Fotin‐Mleczek

et al. 2004

Journal of Biological Chemistry

271

289

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The role of endosomal acidification and retrograde transport for the uptake of the highly basic cell-penetrating peptides penetratin, Tat, and oligoarginine was investigated. The effect of a panel of drugs that interfere with discrete steps of endocytosis or Golgi-mediated transport on uptake and cellular distribution of fluorescein-labeled peptide analogues was probed by confocal microscopy, flow cytometry, and fluorescence spectroscopy of whole cell lysates. The analyses were carried out in MC57 fibrosarcoma cells and in HeLa cells. While MC57 fibrosarcoma cells showed some vesicular fluorescence and a pronounced cytoplasmic fluorescence, in HeLa cells little cytoplasmic fluorescence was observed. In MC57 cells the inhibitors of endosomal acidification chloroquine and bafilomycin A1 abolished the release of the peptides into the cytoplasm. Release into the cytosol preserved endosomal integrity. In addition, cellular uptake of the peptides was inhibited by brefeldin A, a compound interfering with trafficking in the transGolgi network. In contrast, nordihydroguaiaretic acid, a drug that stimulates the rapid retrograde movement of both Golgi stacks and trans-Golgi network to the endoplasmic reticulum, promoted a cytoplasmic localization of Tat peptides in peptide-pulsed HeLa cells. The effects of these drugs on trafficking shared characteristics with those reported for the trafficking of plant and bacterial toxins, such as cholera toxin, which reach the cytoplasm by means of retrograde transport. A sequence comparison revealed a common stretch of 8 -10 amino acids with high sequence homology to the Tat peptide. The structural and functional data therefore strongly suggest a common mechanism of import for cationic cell-penetrating peptides and the toxins.

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Section: Impact Of Golgi-disrupting Agents On the Uptake And Distribumentioning

confidence: 99%

A Stepwise Dissection of the Intracellular Fate of Cationic Cell-penetrating Peptides

Fischer

Köhler

Fotin‐Mleczek

et al. 2004

Journal of Biological Chemistry

271

289

View full text Add to dashboard Cite

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“…It is possible that a certain population of PB arrives at the TGN in a similar fashion to the retrograde trafficking of adeno-associated virus capsids and toxins after endocytosis. 43,44 While this pathway can lead to ER delivery, the inability of BFA to modulate perinuclear and nuclear accumulation suggests that the Golgi to ER retrieval pathway does not contribute to PB trafficking.…”

Section: Penton Base Trafficking a Rentsendorj Et Almentioning

confidence: 99%

Typical and atypical trafficking pathways of Ad5 penton base recombinant protein: implications for gene transfer

et al. 2006

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The adenovirus (Ad) penton base protein facilitates viral infection by binding cell surface integrins, triggering receptormediated endocytosis and mediating endosomal penetration. Given these multiple functions, recombinant penton base proteins have been utilized as non-viral vehicles for gene transfer by our lab and others. Although we have previously demonstrated that penton base-derived vectors undergo integrin-specific binding and cell entry, less than desirable levels of gene expression have led us to re-evaluate the recombinant penton base as an agent for gene delivery. To do so, we have examined here the intracellular trafficking of an Ad serotype 5 (Ad5) recombinant penton base protein (PB). Here, we not only observed that PB utilizes a similar, typical trafficking pathway of whole Ad, but also found that PB entered HeLa cells through pathways not yet identified as contributing to cell entry by the whole virus. We show by high-resolution confocal microscopy and biochemical methods that binding to a v -integrins is a requirement for cell entry, but that early internalization stages did not substantially pass through clathrin-positive and early endosomal compartments. Moreover, a subpopulation of internalized protein localized with caveolin-positive compartments and Golgi markers, suggesting that a certain percentage of proteins pass through nonclathrin-mediated pathways. Similar to the virus, trafficking toward the nucleus was affected by disruption of microtubules and dynein. The majority of penton base molecules avoided the lysosome while facilitating early vesicle release of low molecular weight dextran molecules. In further support of a vesicle escape capacity, a subpopulation of internalized penton base appeared to enter the nucleus, as observed by high-resolution confocal microscopy and cell fractionation. As a confirmation of these findings, we demonstrate that a recombinant penton base facilitated cytosolic entry of an siRNA molecule as observed by RNA interference of a marker gene. Based on our findings here, we suggest that whereas soluble penton base proteins may enter cells through clathrinand non-clathrin-mediated pathways, vesicle escape and nuclear delivery appear to be supported by a clathrin-mediated pathway. As our previous efforts have focused on utilizing recombinant penton base proteins as delivery agents for therapeutics, these findings allow us to evaluate the use of the penton base as a cell entry and intracellular trafficking agent, and may be of interest concerning the development of vectors for efficient delivery of therapeutics to cells. Gene Therapy (2006) 13, 821-836.

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“…caveolin-associated membrane invaginations, that pinch off to form endocytic vesicles and fuse with caveolin-containing membrane compartments, often referred to as caveosomes [3,4,10,11]. Other clathrin-and caveolin-independent pathways are known to exist but are poorly understood due to the lack of known marker proteins [3,4,[12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Endocytosis of influenza viruses

Lakadamyali

Rust

Zhuang

2004

Microbes and Infection

305

267

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Receptor-mediated endocytosis is known to play an important role in the entry of many viruses into host cells. However, the exact internalization mechanism has, until recently, remained poorly understood for many medically important viruses, including influenza. Developments in real-time imaging of single viruses as well as the use of dominant negative mutants to selectively block specific endocytic pathways, have improved our understanding of the influenza infection process.

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NEW EMBO MEMBERS' REVIEW: Entry of ricin and Shiga toxin into cells: molecular mechanisms and medical perspectives

Cited by 238 publications

References 99 publications

A Stepwise Dissection of the Intracellular Fate of Cationic Cell-penetrating Peptides

A Stepwise Dissection of the Intracellular Fate of Cationic Cell-penetrating Peptides

Typical and atypical trafficking pathways of Ad5 penton base recombinant protein: implications for gene transfer

Endocytosis of influenza viruses

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