Diphtheria toxin endocytosis and membrane translocation are dependent on the intact membrane-anchored receptor (HB-EGF precursor): studies on the cell-associated receptor cleaved by a metalloprotease in phorbol-ester-treated cells

Lanzrein, Markus; Garred, Øystein; Olsnes, Sjur; Sandvig, Kirsten

doi:10.1042/bj3100285

Cited by 45 publications

(40 citation statements)

References 29 publications

(32 reference statements)

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“…MMPs are reported to promote cell proliferation by releasing local growth factors stored within the extracellular matrix and process growth factor receptors. 34,35,46 In the present study, however, MMP-2 derived from CD31(Ϫ) CD45(Ϫ) SP cells did not stimulate the proliferation of myoblasts in vivo ( Figure 7D). The factors that stimulate the proliferation of myoblasts remain to be determined in a future study.…”

Section: Mmp-2 Derived From Cd31(ϫ) Cd45(ϫ) Sp Cells Promotes the Migmentioning

confidence: 57%

Muscle CD31(−) CD45(−) Side Population Cells Promote Muscle Regeneration by Stimulating Proliferation and Migration of Myoblasts

Matsuki

Uezumi

Yada

et al. 2008

The American Journal of Pathology

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Section: Mmp-2 Derived From Cd31(ϫ) Cd45(ϫ) Sp Cells Promotes the Migmentioning

confidence: 57%

Muscle CD31(−) CD45(−) Side Population Cells Promote Muscle Regeneration by Stimulating Proliferation and Migration of Myoblasts

Matsuki

Uezumi

Yada

et al. 2008

The American Journal of Pathology

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“…[33][34][35][36] Metalloproteases (MMP) are implicated in the cleavage of proHB-EGF and metalloprotease inhibitors (TIMP) prevent this process. 37 The presence of MMP and TIMP in pterygium is well documented. 38 -42 The interaction between HB-EGF, MMP, and TIMP in pterygia is likely to result in the liberation of the soluble form of HB-EGF from pterygium epithelium.…”

Section: Discussionmentioning

confidence: 93%

The Role of Ultraviolet Irradiation and Heparin-Binding Epidermal Growth Factor-Like Growth Factor in the Pathogenesis of Pterygium

Nolan

DiGirolamo

Sachdev

et al. 2003

The American Journal of Pathology

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Ultraviolet (UV) light is one of the major factors implicated in the pathogenesis of pterygium. The mechanism by which UV light induces this disease remains elusive. The aim of this study was to evaluate the effects of UVB irradiation on the expression of growth factors in cultured pterygium epithelial cells and to demonstrate their distribution within pterygium. We cultured pterygial epithelial cells from pterygium explants and these cells were exposed to 20 mJ/cm 2 of UVB. Total RNA was extracted at 0, 6, and 12 hours after irradiation. 32 P-labeled cDNA was synthesized and analyzed using microarray technology to determine the differential expression of 268 growth factor and cytokine related genes. Semiquantitative reverse transcriptase-polymerase chain reaction was used to corroborate this data. Conditioned media derived from cells exposed to UVB irradiation was analyzed for protein expression by enzyme-linked immunosorbent assay. Immunohistochemistry was used to evaluate the distribution of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in pterygium tissue. Analysis of the hybridization signals revealed that the genes encoding HB-EGF, fibroblast growth factor 3, and cytotoxic trail ligand receptor were consistently elevated at 6 and 12 hours after UVB treatment. HB-EGF mRNA was elevated 6.8-fold at 6 hours after irradiation and was augmented in culture supernatants after the same treatment. Furthermore, HB-EGF reactivity was identified in the epithelium and vasculature of pterygium by immunohistochemistry. HB-EGF was present in normal limbal epithelium, although it was not induced in cultured limbal epithelial cells by UV irradiation. HB-EGF is a potent mitogen, localized in pterygium tissue, and significantly induced by UVB in pterygium-derived epithelial cells. We postulate that this growth factor is a major driving force in the development of pterygia and a means by which UV irradiation causes the pathogenesis of pterygium. (Am J Pathol 2003, 162:567-574) Pterygia are characterized by the encroachment of a wing of altered vascular tissue over the cornea. It is a disorder of epithelial hyperplasia and accompanied fibrovascular growth thought to originate at the corneal-conjunctival junction, where it is proposed that altered limbal stem cells migrate centripetally to encroach on the central cornea.

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“…4B). As an inhibitor control we used diphtheria toxin, which is taken up by clathrin-mediated endocytosis (13). Diphtheria toxin-induced cell rounding of HeLa cells was blocked in the presence of chlorpromazine (Fig.…”

Section: Resultsmentioning

confidence: 99%

The Cytotoxic Necrotizing Factors from Yersinia pseudotuberculosis and from Escherichia coli Bind to Different Cellular Receptors but Take the Same Route to the Cytosol

et al. 2007

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The cytotoxic necrotizing factors CNF1 and CNF2 produced by pathogenic Escherichia coli strains and CNF Y of Yersinia pseudotuberculosis constitutively activate small GTPases of the Rho family. They deamidate a glutamine (Gln63 in RhoA), which is crucial for GTP hydrolysis. CNF1 and CNF Y exhibit 61% identity on the amino acid level, with equal distribution over the whole molecule. Although the two toxins are homologous in the receptor binding domain, we show that they bind to different cellular receptors. CNF Y does not enter Caco-2 and CHO-K1 cells, which are responsive to CNF1. In contrast, HeLa, Hep-2, and HEK 293 cells do respond to both toxins. Competition studies with catalytically inactive mutants of the toxins revealed that binding of CNF1 has no influence on the uptake of CNF Y into HeLa cells. In contrast, uptake of CNF1 is retarded after preincubation of HeLa cells with the catalytically inactive mutant of CNF Y , suggesting that the toxin receptors overlap. Moreover, we compared the pathways of the toxins from receptor binding into the cytosol and showed that both toxins are taken up independent of the presence of clathrin or lipid rafts and are released into the cytosol from acidified endosomes.Cytotoxic necrotizing factor 1 (CNF1) is an AB-type toxin expressed by pathogenic Escherichia coli strains which cause urinary tract infections and neonatal meningitis. CNF1 is a 115-kDa single-chain molecule comprising an N-terminal receptor binding domain and a C-terminal catalytic domain, which contains deamidase activity (for a review, see reference 9). These two domains are separated by a putative translocation domain, which contains two hydrophobic helices involved in membrane translocation (16). CNF1 deamidates small GTPbinding proteins of the Rho family at glutamine 63/61, leading to constitutive activation of the small GTPases by blocking their intrinsic and GTPase activating protein-stimulated GTP hydrolysis (5, 17).CNF1 has been shown to enter cells by receptor-mediated endocytosis independent of clathrin and independent of sphingolipid-cholesterol-rich membrane microdomains (lipid rafts), including caveolae (4). Based on interaction studies, using a yeast two-hybrid system, it has been suggested that cell binding of the toxin is mediated by the laminin receptor precursor p37, a subunit of the mature nonintegrin 67-kDa laminin receptor (3, 11). Moreover, it was shown that CNF1 contributes to E. coli K1 invasion of human brain microvascular endothelial cells via the 67-kDa laminin receptor. Following internalization, CNF1 is delivered to late endosomes by microtubule-dependent transport. From there, it is released into the cytosol in an acidic pH-dependent manner. Specific acidic residues located in the hydrophilic loop, connecting the two hydrophobic helices of the translocation domain, appear to be involved in the translocation process (16).More recently, a cytotoxic necrotizing factor (CNF) produced by Yersinia pseudotuberculosis (CNF Y ) was discovered, which catalyzes the same deamidation reac...

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Diphtheria toxin endocytosis and membrane translocation are dependent on the intact membrane-anchored receptor (HB-EGF precursor): studies on the cell-associated receptor cleaved by a metalloprotease in phorbol-ester-treated cells

Cited by 45 publications

References 29 publications

Muscle CD31(−) CD45(−) Side Population Cells Promote Muscle Regeneration by Stimulating Proliferation and Migration of Myoblasts

Muscle CD31(−) CD45(−) Side Population Cells Promote Muscle Regeneration by Stimulating Proliferation and Migration of Myoblasts

The Role of Ultraviolet Irradiation and Heparin-Binding Epidermal Growth Factor-Like Growth Factor in the Pathogenesis of Pterygium

The Cytotoxic Necrotizing Factors from Yersinia pseudotuberculosis and from Escherichia coli Bind to Different Cellular Receptors but Take the Same Route to the Cytosol

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