Endosomal ricin transport: involvement of Rab4- and Rab5-positive compartments

Moisenovich, M. M.; Tonevitsky, Alexander G.; Maljuchenko, Natalia; Kozlovskaya, N. V.; Агапов, И. И.; Volknandt, Walter; Bereiter‐Hahn, Jürgen

doi:10.1007/s00418-004-0652-6

Cited by 36 publications

(13 citation statements)

References 63 publications

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“…Although the release of endocytosed toxins back into the extracellular medium has been previously described for the plant toxin ricin (88)(89)(90) and for anthrax toxin (91), neither of those toxins has been reported to follow the endocytic recycling route (91,92). The release of endocytosed ricin seems to occur through a mechanism involving exocytosis of multivesicular bodies (89), allowing intoxication of bystander cell populations (90).…”

Section: Discussionmentioning

confidence: 99%

Intracellular Trafficking of AIP56, an NF-κB-Cleaving Toxin from Photobacterium damselae subsp. piscicida

et al. 2014

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f AIP56 (apoptosis-inducing protein of 56 kDa) is a metalloprotease AB toxin secreted by Photobacterium damselae subsp. piscicida that acts by cleaving NF-B. During infection, AIP56 spreads systemically and depletes phagocytes by postapoptotic secondary necrosis, impairing the host phagocytic defense and contributing to the genesis of infection-associated necrotic lesions. Here we show that mouse bone marrow-derived macrophages (mBMDM) intoxicated by AIP56 undergo NF-B p65 depletion and apoptosis. Similarly to what was reported for sea bass phagocytes, intoxication of mBMDM involves interaction of AIP56 C-terminal region with cell surface components, suggesting the existence of a conserved receptor. Biochemical approaches and confocal microscopy revealed that AIP56 undergoes clathrin-dependent endocytosis, reaches early endosomes, and follows the recycling pathway. Translocation of AIP56 into the cytosol requires endosome acidification, and an acidic pulse triggers translocation of cell surface-bound AIP56 into the cytosol. Accordingly, at acidic pH, AIP56 becomes more hydrophobic, interacting with artificial lipid bilayer membranes. Altogether, these data indicate that AIP56 is a short-trip toxin that reaches the cytosol using an acidic-pH-dependent mechanism, probably from early endosomes. Usually, for short-trip AB toxins, a minor pool reaches the cytosol by translocating from endosomes, whereas the rest is routed to lysosomes for degradation. Here we demonstrate that part of endocytosed AIP56 is recycled back and released extracellularly through a mechanism requiring phosphoinositide 3-kinase (PI3K) activity but independent of endosome acidification. So far, we have been unable to detect biological activity of recycled AIP56, thereby bringing into question its biological relevance as well as the importance of the recycling pathway.A IP56 (apoptosis-inducing protein of 56 kDa) is a plasmidencoded toxin of Photobacterium damselae subsp. piscicida (1), a Gram-negative bacterium that infects economically important fish species (2, 3) and is considered one of the most relevant pathogens in mariculture (2-5). In acute infections, a rapid septicemia develops, causing very high mortalities (2, 4, 6). Histopathological analysis of the diseased animals revealed cytotoxic alterations (4, 7-10) that were found to result from pathogeninduced apoptotic death of macrophages and neutrophils (11) and later associated with the activity of AIP56 (1). Indeed, it has been shown that in infected fish, the toxin is systemically distributed and depletes macrophages and neutrophils by postapoptotic secondary necrosis (12), leading to the impairment of the phagocytic defense of the host and consequently favoring P. damselae subsp. piscicida survival and dissemination. Furthermore, the occurrence of a secondary necrotic process in which the phagocytes undergoing apoptosis lyse and release their cytotoxic contents contributes to the genesis of the infection-associated necrotic lesions (12, 13). These observations, together with the fac...

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Section: Discussionmentioning

confidence: 99%

Intracellular Trafficking of AIP56, an NF-κB-Cleaving Toxin from Photobacterium damselae subsp. piscicida

et al. 2014

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“…This protein consists of 2 subunits, binding (B) and catalytic (A). The binding subunit, lectin, is responsible for interaction of the toxin with plasma membrane receptors, its internalization, intracellular transport, and the release from the luminal surface of cell organelles to ribosoma [8,9]. One A-subunit can inactivate up to 1500 ribosomes per minute, which leads to apoptosis activation and cell death.…”

Section: Methodsmentioning

confidence: 99%

Neural Progenitor and Hemopoietic Stem Cells Inhibit the Growth of Low-Differentiated Glioma

Baklaushev

Grinenko²,

Savchenko³

et al. 2012

Bull Exp Biol Med

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The effects of neural progenitor and hemopoietic stem cells on C6 glioma cells were studied in in vivo and in vitro experiments. Considerable inhibition of proliferation during co-culturing of glioma cells with neural progenitor cells was revealed by quantitative MTT test and bromodeoxyuridine incorporation test. Labeled neural progenitor and hemopoietic stem cells implanted into the focus of experimental cerebral glioma C6 survive in the brain of experimental animals for at least 7 days, migrate with glioma cells, and accumulate in the peritumoral space. Under these conditions, neural progenitor cells differentiate with the formation of long processes. Morphometric analysis of glioma cells showed that implantation of neural progenitor and hemopoietic stem cells is accompanied by considerable inhibition of the growth of experimental glioma C6 in comparison with the control. The mechanisms of tumor-suppressive effects of neural and hemopoietic stem cells require further investigation.

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“…Ricin, a ribosome-inactivating protein with lectin properties, binds to various cell surface glycoproteins and glycolipids and is endocytosed via both clathrin-dependent and various clathrinindependent mechanisms (Sandvig and van Deurs 1996;Lord and Roberts 1998;Sandvig et al 2002). Moisenovich et al (2004) were interested in the precise pathway that ricin takes within the endosomal compartment. The small GTPases Rab4, Rab5, and Rab11, which participate in the regulation of endosomal transport in early/sorting endosomes (particularly Rab4 and 5) and the pericentriolar recycling compartment (Rab 11; Trischler et al 1999), were tagged with GFP and transfected into human epidermoid cancer cells A431, where they served as markers for the various endosomal compartments.…”

Section: Traffickingmentioning

confidence: 99%

News and views in Histochemistry and Cell Biology

Asan¹,

Drenckhahn²

2004

Histochem Cell Biol

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Advances in histochemical methodology and ingenious applications of novel and improved methods continue to confirm the standing of morphological means and approaches in research efforts, and contribute significantly to increasing our knowledge about structures and functions in all areas of the life sciences from cell biology to pathology. Reports published during recent months documenting this progress are summarized in the present review.

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Endosomal ricin transport: involvement of Rab4- and Rab5-positive compartments

Cited by 36 publications

References 63 publications

Intracellular Trafficking of AIP56, an NF-κB-Cleaving Toxin from Photobacterium damselae subsp. piscicida

Intracellular Trafficking of AIP56, an NF-κB-Cleaving Toxin from Photobacterium damselae subsp. piscicida

Neural Progenitor and Hemopoietic Stem Cells Inhibit the Growth of Low-Differentiated Glioma

News and views in Histochemistry and Cell Biology

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