Carbohydrate mimicry between human ganglioside GM1 and
            <i>Campylobacter jejuni</i>
            lipooligosaccharide causes Guillain–Barré syndrome

Yuki, Nobuhiro; Susuki, Keiichiro; Koga, Michiaki; Nishimoto, Yukihiro; Odaka, Masaaki; Hirata, Koichi; Taguchi, Kyoji; Miyatake, Tadashi; Furukawa, Koichi; Kobata, Tetsuji; Yamada, Mitsunori

doi:10.1073/pnas.0402391101

Cited by 461 publications

(363 citation statements)

References 31 publications

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“…The process is caused by paralysis of peripheral motor nerves by anti-ganglioside antibodies directed to lipopolysaccharide of Campylobacter jejuni. The major antibodies were identified as directed to GM1 (23). Antibodies causing more serious motor nerve paralysis were found to be directed to heterodimer structures, such as GD1a/GM1, GD1b/ GT1b, and GM1/GT1b, rather than single ganglioside structures (10,24).…”

Section: Discussionmentioning

confidence: 98%

Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway

Todeschini

Santos

Handa

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

115

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Ganglioside GM2 complexed with tetraspanin CD82 in glycosynaptic microdomain of HCV29 and other epithelial cells inhibits hepatocyte growth factor-induced cMet tyrosine kinase. In addition, adhesion of HCV29 cells to extracellular matrix proteins also activates cMet kinase through ''cross-talk '' of integrins with cMet, leading to inhibition of cell motility and growth. Present studies indicate that cell motility and growth are greatly influenced by expression of GM2, GM3, or GM2/GM3 complexes, which affect cMet kinase activity of various types of cells, based on the following series of observations: (i) Cells expressing CD82, cultured with GM2 and GM3 cocoated on silica nanospheres, displayed stronger and more consistent motility inhibition than those cultured with GM2 or GM3 alone or with other glycosphingolipids. (ii) GM2-GM3, in the presence of Ca 2؉ form a heterodimer, as evidenced by electrospray ionization (ESI) mass spectrometry and by specific reactivity with mAb 8E11, directed to GM2/GM3 dimer structure. (iii) Cells expressing cMet and CD82 were characterized by enhanced motility associated with HGF-induced cMet activation. Both cMet and motility were strongly inhibited by culturing cells with GM2/GM3 dimer coated on nanospheres. (iv) Adhesion of HCV29 or YTS-1/CD82 cells to laminin-5-coated plate activated cMet kinase in the absence of HGF, whereas GM2/GM3 dimer inhibited adhesioninduced cMet kinase activity and inhibited cell motility. (v) Inhibited cell motility as in i, iii, and iv was restored to normal level by addition of mAb 8E11, which blocks interaction of GM2/GM3 dimer with CD82. Signaling through Src and MAP kinases is activated or inhibited in close association with cMet kinase, in response to GM2/GM3 dimer interaction with CD82. Thus, a previously uncharacterized GM2/GM3 heterodimer complexed with CD82 inhibits cell motility through CD82-cMet or integrin-cMet pathway.glycosphingolipid ͉ growth factor receptor ͉ ldlD cells ͉ tyrosine kinase G lycosphingolipids (GSLs), including gangliosides, interact with specific membrane proteins, such as growth factor receptors, integrins, tetraspanins (TSPs), and nonreceptor cytoplasmic kinases (e.g., Src family kinases and small G proteins), to form glycosynaptic microdomains controlling GSL-dependent or -modulated cell adhesion, growth, and motility (for review, see refs. 1-3).Our previous studies indicate the following: (i) Ganglioside the GM3/TSP CD9 complex interacts with integrin ␣3␤1 or ␣5␤1 and inhibits motility of CD9-expressing tumor cells (4, 5). (ii) The GM3/CD9/CD81 complex inhibits tyrosine kinase associated with fibroblast growth factor receptor (FGFR) (6) and blocks functional interaction of integrins with FGFR (7). (iii) Enhancement of GM3 or CD9 level in bladder cancer cell line YTS-1 causes reversion to normal phenotype, whereby Src kinase activity is strongly inhibited (8).In contrast to these previous studies, focused on GM3-CD9 interaction that inhibits tumor cell motility, our recent studies (9) addressed the functional role of t...

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Section: Discussionmentioning

confidence: 98%

Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway

Todeschini

Santos

Handa

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

115

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“…This raises the possibility that antiganglioside antibodies and subsequent neuropathies result from cross-reactivity to C. jejuni LPSs via molecular mimicry (48,96,104). Initially, Yuki et al (96,98) reported that the LPS of C. jejuni isolated from a patient with GBS had a GM1-like structure, suggesting that the GM1 epitope-bearing LPS may function in the production of anti-GM1 antibodies in this patient.…”

Section: Oligosaccharides Of Lpss That Mimic Ganglioside Structuresmentioning

confidence: 99%

Ganglioside Molecular Mimicry and Its Pathological Roles in Guillain-Barré Syndrome and Related Diseases

2006

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“…Several reports referred to the antigenic similarity between the components of Campylobacter spp. and peripheral myelin, causing immune-mediated demyelination [12,21,22].…”

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confidence: 99%

Pathological Features of Ganglioradiculitis (Sensory Neuropathy) in Two Dogs

Funamoto

Nibe

Morozumi

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. Canine ganglioradiculitis (sensory neuropathy) was examined pathologically in two dogs (dog Nos. 1 and 2). The affected dogs had 1 and 2 years clinical courses from the onset, respectively. As common clinical signs, both cases showed progressive ataxia, difficulty in prehending food, visual deficit, and several sensory abnormalities. Gross observation after tissue fixation revealed whitish discoloration in the dorsal column of the spinal cords. The histological lesions were mainly distributed in the spinal dorsal roots, ganglions, and dorsal columns. In the spinal dorsal roots and ganglions, there were striking myelin loss, mild infiltration of mononuclear cells, and proliferation of small spindle cells. In the dorsal funiculus, there were moderate to severe diffuse myelin-loss and axonal degeneration. Immunohistochemistry for substance P (SP) revealed marked reduction of SP-immunopositive granules in the spinal substantia gelatinosa of affected dogs. By immunohistochemistry, CD3-positive cells were observed in the dorsal roots of dog No. 2, while CD3-positive cells were rare in those of dog No. 1. In the spinal ganglion of dog No. 1 there were many CD3-and MHC class II-positive cells. By indirect immunofluorescence assay using sera from affected dogs, no autoantibodies against canine nerve tissues were detected. The clinicopathological features of the present cases are almost consistent with those in previous reports of canine sensory neuropathies, while the etiology remains unclear.

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Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain–Barré syndrome

Cited by 461 publications

References 31 publications

Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway

Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway

Ganglioside Molecular Mimicry and Its Pathological Roles in Guillain-Barré Syndrome and Related Diseases

Pathological Features of Ganglioradiculitis (Sensory Neuropathy) in Two Dogs

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