The retromer component sorting nexin-1 is required for efficient retrograde transport of Shiga toxin from early endosome to the trans Golgi network

Bujny, Miriam V.; Popoff, Vincent; Johannes, Ludger; Cullen, Peter J.

doi:10.1242/jcs.003111

Cited by 116 publications

(107 citation statements)

References 58 publications

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“…Another report by Bujny and colleagues in this issue of Journal of Cell Science (Bujny et al, 2007) shows that SNX1 is also required for efficient retrograde trafficking of Shiga toxin. We describe here that, under SNX1-depletion conditions, a shift similar to that observed in Vps26-depleted cells can be detected between STxB and TfR (supplementary material Fig.…”

Section: Discussionmentioning

confidence: 94%

The retromer complex and clathrin define an early endosomal retrograde exit site

Popoff

Mardones

Tenza

et al. 2007

Journal of Cell Science

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Previous studies have indicated a role for clathrin, the clathrin adaptors AP1 and epsinR, and the retromer complex in retrograde sorting from early/recycling endosomes to the trans Golgi network (TGN). However, it has remained unclear whether these protein machineries function on the same or parallel pathways. We show here that clathrin and the retromer subunit Vps26 colocalize at the ultrastructural level on early/recycling endosomes containing Shiga toxin B-subunit, a well-studied retrograde transport cargo. As previously described for clathrin, we find that interfering with Vps26 expression inhibits retrograde transport of the Shiga toxin B-subunit to the TGN. Under these conditions, endosomal tubules that take the Shiga toxin B-subunit out of transferrin-containing early/recycling endosomes appear to be stabilized. This situation differs from that previously described for low-temperature incubation and clathrin-depletion conditions under which Shiga toxin B-subunit labeling was found to overlap with that of the transferrin receptor. In addition, we find that the Shiga toxin B-subunit and the transferrin receptor accumulate close to multivesicular endosomes in clathrin-depleted cells, suggesting that clathrin initiates retrograde sorting on vacuolar early endosomes, and that retromer is then required to process retrograde tubules. Our findings thus establish a role for the retromer complex in retrograde transport of the B-subunit of Shiga toxin, and strongly suggest that clathrin and retromer function in consecutive retrograde sorting steps on early endosomes.

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Section: Discussionmentioning

confidence: 94%

The retromer complex and clathrin define an early endosomal retrograde exit site

Popoff

Mardones

Tenza

et al. 2007

Journal of Cell Science

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150

184

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“…Fluorescent cholera toxin (FITC-Ctx) assays were a modification of experiments previously described (Bujny et al, 2007;Mesa et al, 2005). COS1 cells were transfected with HA-MTMR4 or HA-vector for 24 hours, pre-chilled at 4°C for 10 minutes, and then incubated for 30 minutes in uptake medium (serum-free DMEM, 0.5% BSA, 20 mM HEPES pH 7.2) containing 2 g/ml FITC-Ctx at 4°C.…”

Section: Cholera Toxin Uptake Assaysmentioning

confidence: 99%

The myotubularin phosphatase MTMR4 regulates sorting from early endosomes

Naughtin

Sheffield

Rahman

et al. 2010

Journal of Cell Science

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SummaryPhosphatidylinositol 3-phosphate [PtdIns(3)P] regulates endocytic trafficking and the sorting of receptors through early endosomes, including the rapid recycling of transferrin (Tfn). However, the phosphoinositide phosphatase that selectively opposes this function is unknown. The myotubularins are a family of eight catalytically active and six inactive enzymes that hydrolyse PtdIns(3)P to form PtdIns. However, the role each myotubularin family member plays in regulating endosomal PtdIns(3)P and thereby endocytic trafficking is not well established. Here, we identify the myotubularin family member MTMR4, which localizes to early endosomes and also to Rab11-and Sec15-positive recycling endosomes. In cells with MTMR4 knockdown, or following expression of the catalytically inactive MTMR4, MTMR4C407A , the number of PtdIns(3)P-decorated endosomes significantly increased. MTMR4 overexpression delayed the exit of Tfn from early endosomes and its recycling to the plasma membrane. By contrast, expression of MTMR4 C407A , which acts as a dominant-negative construct, significantly accelerated Tfn recycling. However, in MTMR4 knockdown cells Tfn recycling was unchanged, suggesting that other MTMs might also contribute to recycling. MTMR4 regulated the subcellular distribution of Rab11 and, in cells with RNAi-mediated knockdown of MTMR4, Rab11 was directed away from the pericentriolar recycling compartment. The subcellular distribution of VAMP3, a v-SNARE protein that resides in recycling endosomes and endosomederived transport vesicles, was also regulated by MTMR4. Therefore, MTMR4 localizes at the interface of early and recycling endosomes to regulate trafficking through this pathway.

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“…The clathrin adaptor epsinR was found to be required for transport of Stx to the Golgi, while AP-1 did not seem to be involved [44]. Moreover, coat-like components other than clathrin, such as the retromer complex, has been shown to mediate transport of Stx from early endosomes to the Golgi [67][68][69] (Fig. 2).…”

Section: Endosome-to-golgi Transport Of Stxmentioning

confidence: 99%

“…The retromer consists of the components hVps26, hVps29, hVps35, SNX1, and possibly SNX2 (for review see [70,71]), and this complex has been shown to mediate retrieval of MPRs [51,72] and several other cargo proteins to the Golgi [70]. Importantly, the retromer components hVps26 and SNX1, and also SNX2, are required for endosome-to-Golgi transport of Stx [67][68][69]. Sorting nexins contain a Phox homology (PX) domain that binds to certain phosphoinositides, such as PI(3)P, and a BAR (Bin/Amphiphysin/Rvs) domain that senses or induces membrane curvature.…”

Section: Endosome-to-golgi Transport Of Stxmentioning

confidence: 99%

The Intracellular Journey of Shiga Toxins

Torgersen¹

2013

TOTNJ

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Abstract:The Shiga toxin family consists of Shiga toxin (Stx) that is produced as a virulence factor by Shigella dysenteriae, and the Shiga-like toxins produced by certain strains of enterohemorrhagic E. coli as well as by some other types of bacteria. Infection with bacteria producing these toxins is a threat to human health even in industrialized countries, as the initial diarrhea caused by the infection might be followed by a complication named hemolytic uremic syndrome. The Shiga toxins consist of a binding moiety that in most cases binds to the glycosphingolipid Gb3 on the surface of susceptible cells, and an A-moiety responsible for the toxic effect in the cytosol. In order to reach its cytosolic target, the toxin must be internalized and then transported via the retrograde pathway to the Golgi complex and further to the endoplasmic reticulum. From the endoplasmic reticulum the enzymatically active part of the A-moiety is translocated to the cytosol, and cellular protein synthesis is inhibited. Although the Shiga toxins are involved in disease, they may also be exploited for medical diagnosis and treatment. Interestingly, the toxin receptor, Gb3, has a limited expression in normal tissues, but is overexpressed in several types of cancer. Thus, the use of Shiga toxin, or the binding part of the toxin, has great potential in cancer diagnostics and treatment. Furthermore, studies of the various uptake mechanisms and intracellular transport pathways exploited by the toxins, provide important insight in basic cell biology processes.

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The retromer component sorting nexin-1 is required for efficient retrograde transport of Shiga toxin from early endosome to the trans Golgi network

Cited by 116 publications

References 58 publications

The retromer complex and clathrin define an early endosomal retrograde exit site

The retromer complex and clathrin define an early endosomal retrograde exit site

The myotubularin phosphatase MTMR4 regulates sorting from early endosomes

The Intracellular Journey of Shiga Toxins

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